MANUFACTURE AND REMANUFACTURE OF VOLATILE ANAESTHETIC AGENTS USING SUPERCRITICAL FLUIDS

Abstract

An anaesthetic halocarbon capture system is provided. The system includes a pressure-intolerant sleeve containing filter material for capturing one or more types of anaesthetic halocarbon prior to supercritical fluid extraction, and a pressure-tolerant housing into which the sleeve can be inserted so as to permit exposure of the sleeve contents to pressures required for supercritical fluid extraction.

Claims

1. An anaesthetic agent capture system comprising: a pressure-intolerant inner sleeve for containing filter material for capturing one or more types of anaesthetic agent; and a pressure-tolerant outer tube into which the pressure-intolerant inner sleeve is inserted so as to permit exposure of pressure-intolerant inner sleeve contents to pressures required for extraction of the said one or more types of anaesthetic agent from said filter material; wherein the pressure-intolerant inner sleeve comprises two ends each having an end cap, and wherein the pressure-intolerant inner sleeve is configured to be sealed into the pressure-tolerant outer tube by one or both of the end caps.

2. The anaesthetic agent capture system of claim 1, wherein said pressure-tolerant outer tube is tolerant of supercritical pressures above 73 bar and into which the pressure-intolerant inner sleeve is inserted so as to permit exposure of the pressure-intolerant inner sleeve contents to pressures required for extraction of the anaesthetic agent by supercritical fluid carbon dioxide.

3. The anaesthetic agent capture system of claim 1, wherein the pressure-intolerant inner sleeve is located remotely from the pressure-tolerant outer tube during capture of said one or more types of anaesthetic agent.

4. The anaesthetic agent capture system of claim 1, wherein once the filter material is loaded with captured anaesthetic agent the pressure-intolerant inner sleeve is loaded into the pressure-tolerant outer tube.

5. The anaesthetic agent capture system of claim 4, wherein the pressure-intolerant inner sleeve is configured for mechanical pick up and automated loading into the pressure-tolerant outer tube.

6. The anaesthetic agent capture system of claim 1, wherein the end caps are the same.

7. The anaesthetic agent capture system of claim 1, wherein each cap is mobile on a seal that is capable of moving to engage and seal the pressure-intolerant inner sleeve into the pressure-tolerant outer tube.

8. The anaesthetic agent capture system of claim 1, wherein the system receives exhaust of an anaesthetic circuit.

9. The anaesthetic agent capture system of claim 1, wherein the pressure-intolerant inner sleeve is a stainless-steel tube.

10. The anaesthetic agent capture system of claim 1, wherein the pressure-tolerant outer tube is a stainless-steel tube.

11. A system to capture and anaesthetic agent from a theatre environment and to extract captured anaesthetic agent, the system comprising: equipment to capture anaesthetic agent and equipment to extract anaesthetic agent, wherein the equipment to capture anaesthetic agent is selected from remote from the equipment to extract anaesthetic agent, remote from the theatre environment, or remote from both the equipment to extract anaesthetic agent and the theatre environment.

12. The system of claim 11, wherein the equipment to extract anaesthetic agent is contained within a vehicle whereby to provide a mobile extraction service.

13. The system of claim 12, wherein inner sleeves are filled with anaesthetic agent, a pressure-intolerant inner sleeve is loaded into a pressure-tolerant outer tube in the vehicle and contents of the inner sleeve extracted, then the pressure-intolerant inner sleeve is returned.

14. The system of claim 11, wherein an individual extraction unit is installed in a facility.

15. The system of claim 14, wherein a plurality of pressure-intolerant inner sleeves are filled with anaesthetic agent and automatically loaded into pressure-tolerant housings to extract anaesthetic agent, then the pressure-intolerant inner sleeves are then stored to be taken back to the theatre environment.

16. The system of claim 11, wherein a centralized, joined collection and extraction system is provided.

17. The system of claim 16, wherein anaesthetic gases from multiple theatres are collected onto a filter material of a pressure-tolerant chamber, and the pressure tolerant chamber containing the filter material is connected to an Anaesthetic Gas Scavenging System collecting from multiple theatres.

18. The system of claim 17, wherein two pressure tolerant chambers operate together, one chamber is set to collect anaesthetic exhaust gases and the next chamber is set for extraction.

19. The system of claim 11, comprising a pressure-intolerant inner sleeve for containing filter material for capturing one or more types of anaesthetic agent; and a pressure-tolerant outer tube into which the inner sleeve is inserted so as to permit exposure of pressure-intolerant inner sleeve contents to pressures required for extraction of the said one or more types of anaesthetic agent from said filter material; wherein the pressure-intolerant inner sleeve comprises two ends each having an end cap, and wherein the pressure-intolerant inner sleeve is configured to be sealed into the pressure-tolerant outer tube by one or both of the end caps.

20. The system of claim 11, configured for small consumers such as veterinary practices and small hospital, or configured for large consumers such as tertiary/quaternary hospitals or in cities/regional extraction centers.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0194] Embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings, in which like components are assigned like numerals, and in which:—

[0195] FIG. 1 is a schematic diagram of an anaesthetic machine and breathing circuit according to P34906WO

[0196] FIG. 2 is a schematic diagram of a pressure tolerant capture canister containing a filter material for the capture of anaesthetic halocarbons from the exhaust of a single or many anaesthetic machines as detailed in P34906WO.

[0197] FIG. 3 is a schematic diagram of a system for the extraction and condensation of anaesthetic halocarbon from a capture vessel (be it sleeve contained in a pressure vessel or pressure-tolerant canister) using supercritical fluids, with conservation of gas within the system.

[0198] FIG. 4 is a schematic diagram of a system of purification and condensation of anaesthetic halocarbon by supercritical fluids, with conservation of gas within the system.

[0199] FIGS. 5A-5B show a schematic diagram of a pressure vessel with two different designs of pressure-intolerant sleeve for the capture and extraction of anaesthetic halocarbons from a filter material.

[0200] FIG. 6 is a schematic diagram of a pressure-intolerant sleeve that can be used to capture anaesthetic agent onto a filter material as described in patent P34906WO and in this application. This sleeve is then inserted into a pressure-tolerant chamber for subsequent supercritical fluid extraction of anaesthetic agent from the filter material; and

[0201] FIG. 7 is a schematic diagram of a system for transferring remaining anaesthetic agent dissolved in supercritical fluid from one canister at the end of elution to the next canister.

[0202] FIG. 8 is a schematic diagram of a supercritical fractionation system using an in-series system with the addition of an expansion vessel for the separation and condensation of anaesthetic agents.

[0203] FIG. 9 is a schematic diagram of a supercritical fractionation system using a parallel recirculation system for the separation and condensation of anaesthetic agents.

[0204] FIG. 10 is a schematic diagram of a single stage fractionation column for separating two fractions (Sevoflurane/Isoflurane from Desflurane) by using their respective boiling points, driven by the flow of CO.sub.2.

[0205] FIGS. 11A-11C show a schematic diagram of a housing to collect halocarbons and nitrous oxide intermediates onto a capture material by using the air drawn by a fan in a vehicle or air conditioning unit.

[0206] FIG. 12 is a schematic diagram of a system for manufacturing and purifying sevoflurane from chlorosevoether (chloromethyl 2,2,2-trifluoro-1-(trifluoromethyl)ethyl ether dissolved in supercritical CO.sub.2 reacted with a sterically-hindered tertiary amine hydrofluoride.

[0207] FIG. 13 is a schematic diagram of a system for the manufacture and purification of sevoflurane from hexafluoroisopropanol (HFIP) with equimolar or excess molar concentrations of paraldehyde or trioxane in the presence of aluminium trichloride to form sevochlorane with subsequent fluoro-substitution by potassium fluoride.

[0208] FIG. 14 is a schematic diagram of a system for the manufacture and purification of desflurane from isoflurane and anhydrous hydrogen fluoride or alkali metal fluoride using a suitable catalyst.

[0209] FIGS. 15A-15B show a cooled gas liquid separator for the separation of liquid anaesthetic halocarbon from gaseous carbon dioxide.

[0210] The example embodiments are described in sufficient detail to enable those of ordinary skill in the art to embody and implement the systems and processes herein described. It is important to understand that embodiments can be provided in many alternate forms and should not be construed as limited to the examples set forth herein.

[0211] Accordingly, while embodiment can be modified in various ways and take on various alternative forms, specific embodiments thereof are shown in the drawings and described in detail below as examples. There is no intent to limit to the particular forms disclosed. On the contrary, all modifications, equivalents, and alternatives falling within the scope of the appended claims should be included. Elements of the example embodiments are consistently denoted by the same reference numerals throughout the drawings and detailed description where appropriate.

[0212] Unless otherwise defined, all terms (including technical and scientific terms) used herein are to be interpreted as is customary in the art. It will be further understood that terms in common usage should also be interpreted as is customary in the relevant art and not in an idealized or overly formal sense unless expressly so defined herein.

[0213] All orientational terms are used in relation to the drawings and should not be interpreted as limiting on the invention.

DETAILED DESCRIPTION

[0214] FIG. 2 shows a system 90 for the capture of anaesthetic halocarbons as detailed in P34906WO.

[0215] Exhaust gases from the anaesthetic machine 38 are passed via a conduit 106 through a connector 104 into a canister 100 made of material 103 that is tolerant of supercritical pressures. This canister 100 contains the filter material 102 that captures the anaesthetic agent from the exhaust gases 38. Scrubbed gas then exits the canister via an exit conduit 108 and pipe 110 to pass through a charcoal filter 120 before being exhausted to the atmosphere 122.

[0216] A system 200 to extract and condense anaesthetic halocarbons captured onto a filter material using supercritical fluids is shown in FIG. 3.

[0217] Anaesthetic halocarbons are captured onto a filter material 102 as detailed in FIG. 2 or FIGS. 5A-5B and 6. In FIG. 2, the canister is pressure-tolerant and therefore can be connected to a supply of supercritical fluid directly. In FIGS. 5A-5B and 6, the filter material 102 is contained within a pressure-intolerant sleeve and must be contained within a pressure vessel to extract anaesthetic halocarbons.

[0218] For the purposes of FIG. 3, the vessels 204a, 204b and 204c are either: [0219] 1. A pressure tolerant canister 100 containing anaesthetic halocarbons captured onto a filter material 102. [0220] 2. A pressure intolerant sleeve 501 or 401 containing anaesthetic halocarbons captured onto a filter material 102 inside a pressure tolerant chamber 502 or 402.

[0221] Carbon dioxide gas 239 is supplied from a cylinder 244 at a pressure of 50 bar via a pressure reducing valve 241 to a pressure of 20 bar and solenoid valve 242 under the control of a pressure switch 244. CO.sub.2 passes through the input line 243 to the common line 225 and to the compressor 226a. This increases the pressure and temperature of the CO.sub.2 up to supercritical pressure of 80 bar and temperature of 40 degrees C. Supercritical CO.sub.2 flows through the vessel input line 201 through solenoid valves 202a, b, c through the pressure vessels 204a, b, c containing filter material (not shown) with captured anaesthetic halocarbon. The pressure vessels are contained in a heated chamber 245 at 31-60 degrees Celsius although higher temperatures may be used.

[0222] The supercritical solution of CO.sub.2, anaesthetic halocarbons and any contaminants captured from the anaesthetic exhaust and extracted by supercritical CO.sub.2 passes through output lines 205a, b, c to solenoid valves 206a, b, c and into a common output line 214 to a back pressure regulator 215, set to maintain the pressure vessels at 80 bar. The solution (now at less than supercritical pressure and temperature) passes through the line 216 to an accumulator 217 where a buffer stores pressurized supercritical solution at 40-50 bar under the control of the pressure switch 244 and the CO.sub.2 input solenoid valve 242. If the pressure in the accumulator drops to less than 40 bar, more CO.sub.2 is added to the system by the valve 242 and the pressure increases to 50 bar when the pressure switch 244 closes the input valve 242.

[0223] The solution passes through a transfer line 218 to a pressure reducing valve 219 to a pressure of 10 bar with a very short transfer line 220 or incorporated into a gas-liquid separator 221. This separator is cooled by a thermal jacket to −20 degrees C. (for Sevoflurane/Isoflurane, lower temperatures may be used for Desflurane). Upon depressurization of CO.sub.2 and adiabatic expansion, the temperature in the gas-liquid separator may drop to −30 to −40 degrees Celsius at certain points. The CO.sub.2 remains just above the temperature at which it would condense. The anaesthetic halocarbon condenses and its vapour pressure drops to at or near zero. It is collected by centrifugal and inertial impact into the bottom of the gas-liquid separator. Gaseous CO.sub.2 leaves the gas liquid separator 221 by an exhaust line at the top of the separator 222. A pressure relief valve 245 connected to the exhaust 223 prevents over-pressure of the separator. The CO.sub.2 returns to the compressor 226a by a one way valve 224 and common input line 225 and is returned to the extraction chamber 204a, b, c as described. Therefore, once pressurized, a continuous circle is formed in which the CO.sub.2 is repressurised and recirculated to deliver further extraction. The pressures of the chambers are detected by pressure gauges 213a, b, c and prevented from overpressure by pressure relief valves 212a, b, c via transfer lines 211a, b, c, although these systems may be common.

[0224] Condensed liquid anaesthetic at 10 bar and −20 degrees Celsius at the bottom of the gas liquid separator 221 passes through a transfer line 227 and solenoid valve 228 to a temperature controlled tank 230 becoming stored anaesthetic 250. Initially the tank is at −20 degrees Celsius. A level indicator (not shown) in the tank 230 switches off the solenoid valve 228 to isolate the tank and the tank is depressurised through a pressure reducing valve 233 and flow restrictor 229, feeding CO.sub.2 (and a small amount of anaesthetic agent) back through a transfer line 234 and solenoid valve 235 to a compressor 226c that increases the pressure up from atmospheric pressure to 10 bar, where is passes through a one way valve 238 into the common input line 225. Once the pressure is reduced to atmospheric pressure, the solenoid valve 235 is closed and the tank is warmed up to room temperature gradually with the tank now opened to a reflux condenser 231 that prevents the escape of any anaesthetic halocarbon but allows any remaining CO.sub.2 dissolved in the anaesthetic agent at negative temperatures to escape (not shown). The reflux condenser is maintained at −30 degrees Celsius.

[0225] The system 200 operates in groups of 3 pressure vessels. As an example, one vessel, 204a has finished extraction and 204b and c are full of anaesthetic halocarbon. The flow of CO.sub.2 is stopped into 204a by the solenoid valves 202a and 206a and passes through 204b under the opening of solenoid valves 202b and 206b. The contents of 204a are still pressurized and some anaesthetic halocarbon may remain. The contents of 204c are unpressurised. Therefore, solenoid valves 207a and 210c open and the contents of 204a are transferred down a pressure gradient and then pumped into 204c by the action of the compressor 226b. Vessel 204a is emptied down to a slight vacuum, a relief valve opens (not shown, in similar position to pressure relief valve 212a), and the vessel is equilibrated with the environment. The canister or sleeve can now be changed for another sleeve or canister which is full of anaesthetic halocarbon. Pressure vessel 204c is now pressurized and when 204b has finished being extracted, flow of CO.sub.2 is switched to 204c and a transfer of the remaining contents of 204b to 204a occurs as described above.

[0226] By this cycle, the pressurized contents (CO.sub.2 and remaining anaesthetic halocarbon) are not lost when each sleeve or canister is changed. It is expected that the opening and exchange of sleeves/canisters will be by an automated pick and place system familiar to those skilled in the art of industrial automation.

[0227] FIG. 4 shows a chromatography system 300 that purifies and condenses anaesthetic halocarbon. This system can be used as primary removal of non-halocarbon contaminants or secondary removal of halocarbon contaminants with or without the separation of the individual anaesthetic halocarbons. A modifier may be added to improve separation (not shown).

[0228] Carbon dioxide 239 contained in a cylinder 244 at around 50 bar is transferred by liquid draw 326 to a pump 327 that increases the pressure to 75 bar to supply a backbar 328. Pumps 329a, b, c with non-return valves (not shown) increase the pressure further to 80 to 100 bar and each separately supply an accumulator 331a, b, c respectively and supply line 330a, b, c inside a warmed compartment to 40 degrees Celsius 332. These supply lines each feed a rotary valve 307a, b, c. Extracted liquid anaesthetic halocarbon 250, including certain contaminants, either produced and exhaled by the patient or as anaesthetic agent breakdown products, is supplied from the tank 230 through 40 micron and 15 micron filters 302, 303 and a transfer line to a pump 305. The pump supplies a common input line to each rotary valve 307a, b, c that loads a fixed volume loop of 2-50 mL internal volume. Liquid 250 is returned to the tank in a continuous motion through an outlet in the rotary valve. To load the contents of the loop into the column, the rotary valve 307a, b, c is turned under stepper motor control to the ‘load’ position to link the loop to the CO.sub.2 input 330a, b, c and the chromography columns 309a, b, c via short transfer lines 308a, b, c. This disengages the loop from the flow to and from the tank 230 and the pump 305 stops. After enough CO.sub.2 has passed through the loop to flush the liquid anaesthetic halocarbons 250 onto the columns 309a, b, c, the rotary valves 307a, b, c rotate back to the ‘fill’ position. CO.sub.2 passes through the column without going through the loop to continue chromatography and the loop discharges the CO.sub.2 contained within it to the tank 230, where it is vented through the reflux condenser 231 without the loss of anaesthetic halocarbons, and is refilled with filtered liquid anaesthetic 250 by the pump 305.

[0229] Chromatography proceeds through the columns 309a, b, c. The anaesthetic agent is separated from contaminants (depending on which column is being used). The anaesthetic agents exit the column first into transfer pipe 310, are detected by Infra-red detection 311 and a rotary valve 313 discharges the anaesthetic fraction after passing through the back pressure regulator 312 into a condensation circuit. The condensation circuit starts with a small accumulator 314 leading to a pressure reducing valve 318 to take the pressure down to 10 bar. This leads to a thermally controlled gas liquid separator 221 at −20 to −30 degrees Celsius. Gaseous CO.sub.2 exits the gas liquid separator 221 via transfer pipe 315 to a compressor 316 that increases the pressure to 55 bar and warms the gas to 35 degrees Celsius. The gas then passes through transfer line 319 to through a one way valve 320 and line 321 to the accumulator, completing a loop. This loop may be charged by an input of CO.sub.2 from a tank (not shown), however, once charged, requires no further CO.sub.2. This loop runs continuously, and is added to by injections of anaesthetic halocarbon and CO.sub.2 from the columns as determined by the Infrared sensor 311. Purified liquid anaesthetic halocarbon 251b passes through the transfer line 315 and solenoid valve 316 to a thermally controlled collection tank 230 and when full is depressurised via a flow restrictor 332 and solenoid valve to the compressor 316 to ensure anaesthetic agent is not lost. Once depressurised, the anaesthetic agent may be warmed to remove any remaining CO.sub.2 (depending on the stage in the process) and anaesthetic halocarbon retained by reflux condenser 231.

[0230] Non-anaesthetic waste is diverted by the rotary valve 313 to a capture canister filled with silica and then activated carbon 322 to remove contaminants. This CO.sub.2 is then filtered (not shown), compressed 323 and condensed 324 to return to the cylinder 244 as liquid CO.sub.2 239.

[0231] FIGS. 5A-5B show two different designs of pressure-intolerant sleeve 400a and 400b and a pressure-tolerant vessel 400c into which the sleeve locates for extraction.

[0232] Both sleeves 400a and 400b are made of a stainless steel tube 401. In 400b, this tube is tolerant of supercritical pressures with a minimal factor of safety. In 400a, this tube can be completely intolerant of supercritical pressures. In 400a, the ends are closed by a stainless steel cap 404, containing an egress/ingress port 403. This port is the same at either end but could be different for direction-specific loading. The cap is welded to the stainless tube 401. In 400b, the cap 405 is a plastic insert with a connected stainless steel insert 406 to form the ingress/egress port. This plastic cap 405 is set on seals 406 to connect it to the tube 401. The caps at either end are the same, but could be different if unidirectional loading was required.

[0233] During collection, waste gas 38, enters the sleeve via ingress port 403 which is connected to the waste anaesthetic source by a connector (not shown). The ingress port has an internal lip 402 to facilitate mechanical pick up and automation. The ingress port ends with a mesh 109a containing the filter material 102. This filter material captures the waste anaesthetic halocarbon. Uncaptured gas exits the canister through the mesh 109b and egress port and may be captured onto a charcoal canister (not shown) or enter the scavenging system (not shown) or be directly exhausted as a gas into the atmosphere 122.

[0234] Once loaded with captured anaesthetic halocarbon, the sleeve is loaded into the pressure vessel 400c. The pressure vessel is a stainless steel tube 408 tolerant of supercritical pressures above 73 bar (preferably 100-400 bar although higher pressure tolerance could be used). This tube is sealed 409 and screws into a base 410 with a moulded insert 407 that houses the cap of the sleeve 400a or 400b. When using sleeve 400a, a small channel is provided through the moulding 407 to allow the outside of the sleeve to pressurize (not shown). The other end of the tube 408 is sealed 412 with a lid 415 that fits by bayonet fitting 413 onto the tube 408. A moulding 406 in the lid houses the cap of the sleeve 400a or 400b with channels 416 to allow the passage of CO.sub.2. The base 410 and lid 415 have channels 416 through the stainless steel and mouldings to allow the passage of CO.sub.2. Two inlet 411a and 411b and two outlet 414a and 414b are provided although fewer or more can be used. Flow can be either from 411(a or b) to 414(a or b) or from 414(a or b) to 411(a or b).

[0235] In the case of sleeve 400b, when pressurized, the cap 405 moves on the seal 406 upwards and compresses itself into the pressure vessel mouldings 406, 407. These mouldings have a seal at either end (not shown) to seal the sleeve into the moulding. Therefore, flow only goes through the sleeve and not around the sleeve as it does with 400a. The cap is retained by the mouldings and the tube 401 is pressure-tolerant and maintained within the pressure vessel for safety. This system prevents exposure of the outside of the sleeve to supercritical CO.sub.2 and possible incorporation of chemicals on the external sleeve surface into the flow of anaesthetic halocarbon. However, it allows the use of a sleeve that would not be able to withstand pressure on its own and can therefore be made of thinner, cheaper, bulk produced materials that ensure that the sleeves are cost-effective.

[0236] A system 500 to capture and elute anaesthetic agent from the anaesthetic machine and theatre environment 38 is shown in FIG. 6.

[0237] Anaesthetic agent and waste gases 38 enter a pressure-intolerant sleeve 501 from standard scavenging piping 505 coupled to an ingress conduit 506a. The ingress conduit 506a screws into threading incorporated into the sleeve 501. Anaesthetic gas flow is dispersed into the container by baffles 507 made of plastic or metal that does not absorb/react with anaesthetic gases or supercritical fluids. The waste gases 38 then pass through an intake mesh 109a into the filter material 102, which captures the anaesthetic agent from the waste gas flow 38. Waste gases depleted of anaesthetic agent then pass through the exit mesh 109b and are directed to the egress conduit 506b by baffles 507. Waste gases then pass from the egress conduit 506b into standard scavenging piping 505 for subsequent extraction to the environment 122.

[0238] Extraction requires pressures above the critical pressure of carbon dioxide 72.9 bar, therefore a chamber made of a suitable material, preferably stainless steel, and designed to tolerate these pressures is required. This chamber 502 is divided into two portions that are reversibly connected, preferably by a machined thread 508 and sealing washers 509a and 509b, so that the pressure-intolerant sleeve 501 could be inserted into the pressure-tolerant chamber 502 and the chamber sealed for supercritical fluid extraction. Supercritical fluid 203, preferably carbon dioxide, enters the chamber through a standard ⅛.sup.th inch ingress piping 510a through intake conduit 511a. The chamber has a recess 512a and 512b with sealing washers 513a and 513b. The recesses 512a and 512b tightly fit the intake sealing rings 504a and 504b respectively on the pressure-intolerant sleeve 501 when in the chamber and prevent supercritical fluid from bypassing the sleeve 501 and the filter material 102.

[0239] For extraction, both portions of the pressure-tolerant chamber 502 are placed around the pressure-intolerant sleeve 501 with the intake sealing rings 504a and 504b located within their recesses 512a and 512b. As the chamber is closed, pressure is generated that seals the pressure-intolerant canister against sealing washers 5I 3a and 513b to prevent supercritical fluid 203 from bypassing the filter material 102 contained in the sleeve 501. Supercritical fluid 203 is passed into the chamber 502 and sleeve 501 through ingress standard piping 510a and ingress conduit 511a. Supercritical fluid 203 traverses the intake mesh 109a and passes through the filter material 102, dissolving anesthetic agent captured from the waste gases 38. This supercritical solution passes through the exit mesh 109b to the egress conduit 511b and egress piping 510b for subsequent purification by chromatography or fractional separation as described in patent application P34906WO.

[0240] A system for the loading and unloading of supercritical fluid 600, preferably carbon dioxide, into sequential chambers to conserve carbon dioxide, anaesthetic agent and energy is shown in FIG. 7.

[0241] Carbon dioxide 601 contained in a cylinder 602 is pumped 603 into an accumulator 604 in a temperature controlled environment 605, above the critical temperature of carbon dioxide 31.1 degrees centigrade. Carbon dioxide 203 flows into a limb of the elution circuit via open valve 606a while valve 606b is closed. Carbon dioxide passes into a pressure-tolerant chamber 502a containing a pressure-intolerant sleeve 501a filled with filter material 102 that has absorbed anaesthetic agent. The chamber pressurizes above the critical pressure of carbon dioxide (72.9 bar) under the influence of a back-pressure regulator 608 situated downstream that keeps the circuit closed until a controllable pressure above the critical pressure is achieved.

[0242] Once the set pressure is achieved, the back pressure regulator 608 opens and supercritical CO.sub.2 flows through the filter material 102 contained in the sleeve 501a, extracting the anaesthetic agent via the open valve 607a. Valve 607b is closed to prevent the passage of gas into the second chamber 502b and sleeve 501b. The supercritical solution 203 is then available for purification by supercritical fluid chromatography and/or fractional separation as described in P34906WO and this application.

[0243] The eluted anaesthetic agent concentration drops in an exponential decay and is measured by infrared spectroscopy 609 from feed 611a. When a set threshold is reached as determined by the controller 610 via feed 612a from IR detection 609, a signal 613a is sent to valve 607a and 606 a (not shown) to close these valves. The controller then sends a signal (not shown) to the pump 614 that initiates the transfer of CO.sub.2 and remaining anaesthetic agent from the first chamber 502a and sleeve 501a to the next chamber 502b and sleeve 501b. This transfer will initially be down a pressure gradient and will be passive, but will require energy after the gradient has equilibrated. When the pressure in the sleeve 501a and chamber 502a has reached atmospheric pressure, the pump 614 is stopped and flow discontinued.

[0244] The controller then signals (not shown) to valves 606b and 607b to open. Pressure in the circuit will have been maintained above critical pressure as the back pressure regulator 608 will have remained closed after flow through the first chamber 502a had ceased and the pressure dropped below the set-point for the valve to open. Once valves 606b and 607b are open, supercritical CO.sub.2 will flow through the second chamber 502b and sleeve 501b, dissolving and extracting anaesthetic agent from the filter material 102. The supercritical solution 203 from chamber 502b is then available for purification by supercritical fluid chromatography and/or fractional separation as described in P34906WO and this application.

[0245] The system 600 has the benefit of not wasting remaining anaesthetic agent after elution/extraction has reached a set point. Therefore, the anaesthetic agent concentration set-point at which elution finishes can be set higher and high concentrations of anaesthetic agent can be maintained in the supercritical solution for subsequent chromatography steps. As chromatography purification is the rate-limiting step, this has a significant impact on efficiency. The system 600 also saves some of the energy and CO.sub.2 required to pressurize the chambers, significantly reducing costs and environmental impact.

[0246] The system 700 shown in FIG. 8 shows an in-series fractional separation and condensation system, including an expansion chamber and CO.sub.2 recirculation, driven by the depressurization of supercritical CO.sub.2, referred to as supercritical fractionation in P34906WO.

[0247] Carbon dioxide 201 from a pressurised cylinder 202 is fed to a pump 206a, increasing pressure to a set point above the critical pressure of CO.sub.2 (72.9 bar). This fluid passes to an accumulator 208 in a temperature-controlled environment (not shown) above the critical temperature of CO.sub.2 (31.1 degrees C.). The supercritical CO.sub.2 from the accumulator passes into the elution and chromatography systems as described in P34906WO and this application. The supercritical CO.sub.2 is used to elute/extract anaesthetic agent from a capture filter material and then purify it by multiple column supercritical fluid chromatography. Infra-red spectroscopy selects peaks corresponding to pure anaesthetic agent and these are delivered via a back pressure regulator to an expansion vessel 701. Another direct feed of CO.sub.2 from the accumulator 208 is delivered to the expansion vessel 701 passing through a variable pressure-reduction valve 702 and safety valve 703a that protects the downstream circuit from supercritical pressures. Aliquots of a mixture of anaesthetic agents and gaseous CO.sub.2 are delivered to the expansion vessel 701 when peaks are selected by IR spectrophotometer. The volume of the expansion vessel 701 and the direct flow of CO.sub.2 from the accumulator 208 buffer this intermittent flow to produce a continuous flow of a mixture of anaesthetic agents carried in gaseous CO.sub.2 from the expansion vessel 701 via an egress pipe 704. This mixture passes to the first fractionating column 652a containing inert beads 661 to turbulate flow and improve heat transfer for inertial condensation. The mixture is held at a pressure determined by a downstream pressure-reducing valve 205a. The pressure slows the flow of gases through the column to improve heat transfer and condensation of the anaesthetic gases. As this column is intended to selectively condense the least volatile anaesthetic agent, it is heated to prevent the more volatile fraction from condensing. This is by thermal sleeve 662a and a temperature-controlled environment 705a. The column temperature is measured by thermocouples 706a, 706b with readouts 707a and 707b respectively. The least volatile fraction 12x condenses and is collected by the opening of a needle valve 708a under computer control (not shown). The liquid anaesthetic agent passes into an expansion chamber 709a which increases its volume to maintain atmospheric pressure. The chamber 709a is maintained in a cold sleeve 712a to keep the purified anaesthetic agent 12x in liquid form while dissolved CO.sub.2 is released for venting 710a. It is then checked for purity using gas chromatography-mass spectrometry (GC-MS) and bottled (not shown). Alternatively the liquid can be collected into a temperature controlled collection and depressurisation system as shown in FIGS. 3 and 4.

[0248] The more volatile anaesthetic agent and gaseous CO.sub.2 leave the column 652a via an egress pipe 711a to the pressure-reducing valve 205a and an IR sensor 160 to ensure the absence of the least volatile fraction. The mixture passes into the second fractionation column 652b held at a lower pressure than the first fractionation column by a pressure reduction valve 205b. The second fractionation column is cooled by a temperature-controlled environment 705b and thermal sleeve 662b. Column intake and exit temperatures are measured by thermocouples 706c and 706d with respective readouts 707c and 707d. The condensed fraction 12y is collected at the bottom of the column and is transferred to an expansion chamber 709b by needle valve 708b under computer control (not shown). This chamber is cooled using a thermal sleeve 712b to keep the anaesthetic agent liquid while the gaseous CO.sub.2 is vented 710b. Alternatively the liquid can be collected into a temperature controlled collection and depressurisation system as shown in FIGS. 3 and 4.

[0249] The pure CO.sub.2 leaves the fractionation column 652b via the pressure-reducing valve 205b and IR chamber 160b to pass either back to the expansion chamber via a pump 206b to reduce the need for CO.sub.2 via the direct feed from the accumulator 208. Thereby the direct feed is replaced by the recirculated feed. If the pressure in the circuit rises above a set threshold, pure CO.sub.2 is vented to the environment 122 via a pressure safety valve 703b and vent 660.

[0250] Further purification can be achieved by fractional distillation (not shown).

[0251] The system 800 shown in FIG. 9 details a parallel anaesthetic agent fraction collection system using the sequential depressurization of CO.sub.2, so called supercritical fractionation in patent P34906WO.

[0252] Carbon dioxide 201 stored in a pressurised cylinder 202 is fed to a pump 206a to raise the pressure to a set point above the critical pressure of CO.sub.2 (72.9 bar). This is then fed to an accumulator 208 in a temperature-controlled environment (not shown) above the critical temperature of CO.sub.2 (31.1 degrees C.). The supercritical CO.sub.2 from the accumulator passes into the elution and chromatography systems as described in P34906WO and this application. The supercritical CO.sub.2 is used to elute anaesthetic agent from a capture filter material and then purify it by multiple column supercritical fluid chromatography. Infra-red spectroscopy selects peaks corresponding to pure anaesthetic agent and these are delivered via a back pressure regulator to an expansion vessel 701. Another direct feed of CO.sub.2 from the accumulator 208 is delivered to the expansion vessel 701 passing through a variable pressure-reduction valve 702 and safety valve 703 that protects the downstream circuit from supercritical pressures. Aliquots of a mixture of anaesthetic agents and gaseous CO.sub.2 are delivered to the expansion vessel 701 when peaks are selected by IR spectrophotometer. The volume of the expansion vessel 701 and the direct flow of CO.sub.2 from the accumulator 208 buffer this intermittent flow to produce a continuous flow of a mixture of anaesthetic agents carried in gaseous CO.sub.2 from the expansion vessel 701 via an egress pipe 704 to a computer controlled valve 713a. This directs the mixture into the first fractionation column 652a containing inert beads 661 under a pressure set by the back pressure regulator 205a. The column is heated to prevent the condensation of the more volatile fraction of anaesthetic gas. This is achieved by the column being in a temperature-controlled environment (not shown) and being surrounded by a thermal sleeve 662a. Column temperature is measured by thermocouples 706a and 706b and read-outs 707a and 707b. The less volatile fraction 12x condenses and is collected at the bottom of the fractionation column 652a. It is released into an expansion chamber 709a via a needle valve 708a under computer control (not shown). The expansion of the chamber volume ensures that pressure remains at atmospheric pressure. The anaesthetic agent is cooled by a thermal sleeve 712a to prevent the anaesthetic agent vapourising as the CO.sub.2 dissolved in the anaesthetic agent is vapourised. This CO.sub.2 is vented 710a.

[0253] The column is set up to ensure that none of the more volatile fraction is collected at the expense of the possibility that not all the less volatile fraction is collected. Therefore, gas exiting the first fractionating column 652a is checked by IR 160 and if some of the less volatile fraction remains, it is passed back to a pump 206b and delivered to the expansion chamber 701 to go back through the valve 713a and into the first fractionation column 652a again. By multiple passes through the first fractionation column, complete condensation of the less volatile anaesthetic agent should be achieved without contamination by the more volatile fraction.

[0254] When all the less volatile fraction has been condensed, a controller (not shown) closes valve 713a and opens valve 713b, passing the CO.sub.2 and the more volatile fraction into the second fractionating column 652b. This is at a pressure controlled by the back pressure regulator 205b. The temperature of the column is −30 to −20 degrees Celsius, controlled by a temperature-controlled environment (not shown) and thermal sleeve 662b and measured by thermocouples 706c, 706d and read-outs 707c and 707d respectively. The more volatile fraction condenses 12y, leaving gaseous pure CO.sub.2 to pass out of the column. The fraction 12y collects at the bottom of the column and passes into an expansion chamber 709b via a needle valve 708b under computer control (not shown). The expansion of the chamber volume ensures that pressure remains at atmospheric pressure. The anaesthetic agent is cooled by a thermal sleeve 712b to prevent the anaesthetic agent vapourising as the CO.sub.2 dissolved in the anaesthetic agent is vapourised. This CO.sub.2 is vented 710b. It may be that some anaesthetic agent remains with the gaseous CO.sub.2. This is detected by the IR detector 160b after passing through the pressure-reducing valve 205b. This signals to a controller (not shown) that recirculates the gases back to a pump 206b and the expansion chamber 701 to pass through the column 652b again and complete condensation over one or more cycles.

[0255] One advantage of system 800 over system 700 is that a pressure-reduction is not required between the first and second fractionation columns. By using a parallel system, the pressure and temperatures can be independently altered to condense the different agents at easily attainable temperatures and flow rates.

[0256] A further advantage of the preferred embodiment is that system 800 allows for incomplete condensation which is a likely occurrence. By using recirculation, system 800 can carefully and completely condense individual fractions of anaesthetic agent.

[0257] FIG. 10 shows a single column schematic for the separation of different anaesthetic halocarbons by virtue of their different volatilities as shown in system 900.

[0258] Carbon dioxide 201 from a cylinder 202 and pipe 901 is pumped 902 via pipe 903 into an accumulator 904 at supercritical pressures. This may feed chromatography or elution steps as described in this patent as well as this current use (not shown). CO.sub.2 passes through a transfer line 905 to a pressure reducing valve 906 reducing the pressure to 40-50 bar and one way valve 908 into another accumulator 910 under pressure relief valve 907 to prevent system over-pressure.

[0259] The accumulator is fed with anaesthetic from the chromatography or elution systems 909 as described above. The accumulator buffers the pressures in the system and feeds the mixture of CO.sub.2 and anaesthetic halocarbon through a transfer line 911 to a pressure reducing valve 912 dropping the pressure to 2-10 bar immediately adjacent to or incorporated into the fractionation column 913 under the protection of a pressure relief valve 915. The pressure drop and adiabatic expansion cause the temperature of the gas to drop to −20 to −30 degrees Celsius. Both anaesthetic fractions 12x and 12y condense in the column and pass by gravity down the column 913. The column is temperature controlled by thermal sleeve (not shown) into three separate zones 914a, b, c. The temperature of zone 1, 914a, is near the boiling point of the less volatile fraction, in this case Desflurane at 23 degrees Celsius. Thus, Sevoflurane or Isoflurane (fraction 12x) will collect and be available for removal and final removal of CO.sub.2 as described elsewhere in this application by the pipe 918a. The Desflurane boils and passes back up the column through zone 2, held at an intermediate temperature between the boiling point of Desflurane and the temperature at which the saturated vapour pressure of Desflurane is zero (around −30 degrees Celsius). The Sevoflurane/Isoflurane condenses and passes back down the column. The Desflurane proceeds up to zone 3, at a temperature of −20 to −30 degrees Celsius, where the Desflurane condenses and is removed by transfer line 918b to form fraction 12y. Gaseous CO.sub.2 leaves the column and passes to a compressor 916 where it is re-pressurised to 40-50 bar and passes back via pipe 917 to the accumulator 910 to form a continuous loop, to reduce the need for input from the cylinder CO.sub.2. This may be under microprocessor control (not shown).

[0260] FIGS. 11A-11C show a system 800a and 800b demonstrating a front (800a) and side view (800b) of a fan 805 in assembly 806 behind an enclosure 802 filled with filter material 102. The enclosure is fitted so that air flow 807 passes through the enclosure. This could be arranged so that air passes from the fan to the enclosure or from the enclosure to the fan (as shown in 800b) depending on available configurations.

[0261] Diagram 800c and d show the side 800c and front view 800d of the enclosure 802, with the front and back of the enclosure being made of a wide-grid mesh 803 supporting a fine mesh 804 capable of containing the capture material 102. The enclosure shape and size would depend on what fan unit it was to be attached to and would be made to ensure that the resistance to airflow of the mesh and capture material did not reduce airflow to the machine excessively.

[0262] System 900 for the manufacture of sevoflurane from chlorosevoether is shown in FIG. 12. Carbon dioxide 201 contained in a cylinder 202 passes through a pump 206 to increase the pressure above the critical pressure of CO.sub.2 (72.9 bar). The fluid enters an accumulator 208 in a temperature-controlled environment (not shown) above the critical temperature of CO.sub.2 (31.1 degrees Centigrade). The supercritical CO.sub.2 leaves the accumulator 208 via egress conduit 209 into the reaction chamber 210 made of a pressure and temperature tolerant material, preferably although not exclusively stainless steel or aluminium, and coated in an inert material, preferably but not limited to Teflon, polyimide, polyethylene napthalate or another material that does not react with fluoroethers or supercritical carbon dioxide. Chlorosevoether 211 contained in an inert vessel 212a is injected into the reaction vessel 210 by a high pressure pump (not shown) and injector 207a under the signal 214 of a controller 213. This controller is influenced by the output 215 of a detector 216, preferably UV, MS, PAS or ARS but most favourably IR spectroscopy. Further reagent, in the form of a tertiary amine hydrofluoride salt 217 contained in an inert container 212b is injected into the reaction vessel 210 by a high-pressure pump (not shown) and injector 207b under the influence of the controller 213 (not shown). The reaction proceeds inside the reaction vessel at temperatures above the critical temperature of carbon dioxide (31.1 degrees Centigrade) and at pressures above the critical pressure of carbon dioxide (72.9 bar). Products and reactants proceed through the chamber under the flow of supercritical CO.sub.2 and reactants. This delivers the supercritical solution 218 to the detector 216 to regulate the input of reagent and reaction conditions. The reaction temperature can be altered by changing the temperature of the environment, although it must remain above the critical temperature of CO.sub.2. The pressure of the reaction can be altered by the controller influencing the pump 206. The supercritical solution 218 is delivered to chromatography and/or fractional separation modules as shown in FIG. 4, 8, 9 or 10.

[0263] The system 1000 shows the process of manufacture of sevoflurane from hexafluoroisopropanol (HFIP) in FIG. 13. Carbon dioxide 201 contained in a pressurised cylinder 202 is transferred above critical pressure (72.9 bar) by a pump 206 and passed into an accumulator 208 in a temperature controlled environment (not shown) above the critical temperature of carbon dioxide (31.1 degrees Centigrade). Supercritical CO.sub.2 passes into a first reaction chamber 210a made of a pressure and temperature tolerant material, preferably although not exclusively stainless steel or aluminium, and coated in an inert material, preferably but not limited to Teflon or another material that does not react with fluoroethers or supercritical carbon dioxide. HFIP 219 in an inert container 212a is fed into the reaction chamber by a high-pressure pump (not shown) and injector 207a under the signal 214a from a controller 213. Formaldehyde, preferably paraformaldehyde or trioxane 220 contained in an inert container 212b, in equimolar or molar excess quantities are also fed into the first reaction chamber 210a by high-pressure pump (not shown) and injector 207b under the control of the controller 213 (signal not shown). The supercritical solution 218 passes from the reaction chamber via a detection device 216a preferably UV, MS, PAS or ARS but most favourably IR spectroscopy into a second reaction chamber 210b containing aluminium trichloride to produce sevochlorane dissolved in supercritical CO.sub.2. The products pass through a second detector 216b into a third reaction chamber 210c in which potassium fluoride 222 contained in an inert container 212c and dissolved in water is fed into the chamber by high-pressure pump and injector 207c. Water will quench the reaction of any remaining aluminium hydroxydichloride with sevochlorane. Alternatively solid potassium fluoride could be present inside the third reaction vessel 210c. Sevochlorane reacts with the fluorine-donor to produce sevoflurane. Products leave the third reaction chamber to further supercritical chromatography or fractionation for example as shown in FIG. 4, 8, 9 or 10.

[0264] The system 1100 shown in FIG. 14 shows a method for the manufacture of desflurane from isoflurane and a fluorine donor, preferably potassium fluoride, sodium fluoride or anhydrous fluorine. Carbon dioxide 201 contained in a pressurised cylinder 202 is transferred above critical pressure (72.9 bar) by a pump 206 and passed into an accumulator 208 in a temperature-controlled environment (not shown) above the critical temperature of carbon dioxide (31.1 degrees Centigrade). Supercritical CO.sub.2 passes into a first reaction chamber 210a made of a pressure and temperature tolerant material, preferably although not exclusively stainless steel or aluminium, and coated in an inert material, preferably but not limited to Teflon or another material that does not react with fluoroethers or supercritical carbon dioxide.

[0265] Isoflurane 224 contained in an inert container 212a is injected into the reaction vessel by high-pressure pump (not shown) and injector 207a, dissolving into the supercritical CO.sub.2. A fluorine donor 223, preferably hydrogen fluoride, potassium fluoride, sodium fluoride or anhydrous fluorine, contained in an inert container 212b is injected into the reaction chamber 210a by a high-pressure pump and injector 207b. Alternatively the potassium fluoride may be present as a granular solid in the reaction vessel 210a. The fluoro-transfer reaction may proceed without catalysis, but may require transfer of the reactants into a second reaction chamber 210b, containing a catalyst 225, preferably but not limited to antimony pentahalide, a transition metal trifluoride (for example cobalt trifluoride), transition metal oxide (such as chromia) or mixed with a phase transfer catalyst such as tetramethylammonium chloride. In a preferable embodiment, these catalysts are present inside the reaction chamber 210a with the potassium fluoride, removing the need for a second reaction chamber 210b. Products including desflurane pass through a detection device 216 preferably UV, MS, PAS or ARS but most favourably IR spectroscopy that relays 215 to a controller 213 to signal 214 and regulate the pump 206 pressures (not shown), the temperature (not shown) and the injectors 207a (not shown) and 207b to control the flow of reactants and solvent into the reaction vessel 210a. The products then pass into the supercritical chromatography and/or fractionation systems for example as shown in FIGS. 4, 8, 9 and 10.

[0266] A device for the separation of liquid anaesthetic halocarbons from gaseous CO2 is shown in FIGS. 15A-5B, with a top view of the inlet 1200a and a side-view cutout of the entire device 1200b.

[0267] The mixture of CO2 and anaesthetic agents (plus contaminants depending on the stage of the process that the device is being used in) is depressurised immediately adjacent to the gas liquid separator (GLS) 1200a, b. The gas mixture enters the GLS via a input connector 1201, the gas entering a circular chamber 1202 with three eccentric injector ports 1203 that pass from the circular chamber 1202 into the cyclonic chamber 1204. The cyclonic chamber is a tube with a tapered central pipe 1205 that ensures that the upper portion of the chamber sectional area is small, so that when combined with the eccentric injection of the gas mixture, it forms a cyclonic motion. As the mixture is decompressed through the pressure reducing valve before the GLS (not shown) and the narrow eccentric inlet ports 1203, it undergoes adiabatic expansion and cools to −20 to −30 degrees Celsius. The anaesthetic halocarbon condenses and is passed onto the outer surface 1206 of the cyclonic chamber 1204 by the cyclonic rotation of the CO2 gas. This outer surface 1206 is cooled to −20 to −30 degrees Celsius by a thermal jacket 1207 that contains a coolant such as Polyethylene Glycol 1208 cooled by connection 1209 to an external chiller unit (not shown). The jacket is sealed top 1210a and bottom 1210b and held in place against the injector assembly 1211 by a screw on lower element 1212.

[0268] The CO2 gas passes down the cyclonic chamber (arrow 1213), the sectional diameter increases and the gas velocity slows until it reaches cooled glass beads 1214 that provide inertial condensation and also protect condensed anaesthetic halocarbon that has passed down the outer surface 1206 from exposure to further rapid gas flow. The beads are held in place by a mesh 1215 that covers the outlet 1216. CO2 gas then passes up the tapered central pipe 1205 (arrow 1217), past the coldest area of the GLS near the injection and expansion point of the gas mixture 1211, leading to further condensation. The gas velocity in the central tapered pipe is such that a bead of liquid will be able to run down the inner surface of the pipe 1205. CO2 gas exits the central pipe (arrow 1218) in the uppermost section 1219 and leaves the assembly by a connector 1220 for subsequent recompression and re-use. The entire assembly is pressure tolerant with working pressure of up to 20 bar for areas exposed to the CO2. This pressure is maintained by a pressure-relief valve (not shown) located following the gas outlet 1220. Temperature in the GLS is monitored by thermocouples 1221a, b, c. The liquid outlet 1216 passes to a output pipe 1222 (only the start is shown), that is subsequently connected to a valve (not shown). The GLS can be completely disassembled for cleaning and quality control checks as required. The main body of the GLS is made from 316 stainless steel, the injector section 1211 is made from anodised aluminium and the thermal jacket is made from PTFE (Polytetrafluoroethylene) with a stainless steel cover, however other suitable materials could be used known to those skilled in the art.

Experimental Information

[0269] A 316 stainless steel 1 Litre internal volume capture sleeve containing plain silica gel granules (0.5-1 mm) was connected to the anaesthetic exhaust, before a charcoal canister in a veterinary medical environment. The capture vessel was in place for 7 working days and gained 118 g of weight. Expected anaesthetic consumption during this period was 80-130 g during normal use. Anaesthesia consisted of 2 L/min oxygen with 2% sevoflurane via veterinary circle system and soda lime CO.sub.2 absorber.

[0270] The contents of the sleeve were extracted using supercritical CO.sub.2 at 80 bar and 50° C. for 90 minutes with >90% of product produced during the first 40 minutes.

[0271] Gas liquid separator jacket temperature was controlled at −20° C. Input pressure to pressure reducing valve before gas-liquid separator was 40-50 bar set by digital pressure switch regulating solenoid input from CO.sub.2 cylinder (44-50 bar). Pressure reduced to 10 bar in gas liquid separator. Gas input temperature −21 to −32° C. with gas output temperatures of −14 to −20° C.

[0272] Carbon dioxide was recirculated by a Haskel AG-30 single stage, lubrication free gas booster with air drive pressure of 6 bar.

[0273] 100-105 mL of product was recovered. Gas Chromatography-FID showed purity of 99.7%, Gas Chromatography-Mass Spectrometry showed major contaminant as HFIP (Hexafluoroisopropanol).

[0274] Example chromatography separation results for demonstration using JASCO PU-2080 SFC equipment with UV or IR detection:

[0275] Separation of Common Exhaled Contaminants:

[0276] Cyano column 100 mm length, 21 mm ID—flow 20 mL/min, 80 bar, 55° C., 2 mL injection volume

[0277] Sevoflurane and Isoflurane—0.4-1.5 min

[0278] Ethanol 0.1%-6-9 mins

[0279] Methanol 0.1%-7.5-9 mins

[0280] Acetone 0.05%-3-4 mins

[0281] Separation of HFIP from Anaesthetic Agents:

[0282] Cyano column 250 mm length 4.6 mmID—flow 0.5 mL/min, 80 bar, 40° C., 10 microlitre separate injection volume

[0283] Isoflurane/Sevoflurane 7.5 min-10.5 min

[0284] HFIP 16-35 mins

[0285] Separation of Sevoflurane from Isoflurane:

[0286] DEAP 2×250 mm 4.6 mmID flow rate 2.9 ml/min CO.sub.2, 0.1 ml/min ethanol, 80 bar, 40° C., injection 50:50 isofluorane:sevoflurane, 10 microlitres volume.

[0287] Sevoflurane 2.2-2.5 mins

[0288] Isoflurane 2.7-3.1 min

[0289] Although illustrative embodiments of the invention have been disclosed in detail herein, with reference to the accompanying drawings, it is understood that the invention is not limited to the precise embodiment shown and that various changes and modifications can be affected therein by one skilled in the art without departing from the scope of the invention as defined by the appended claims and their equivalents.