Method and device for safely generating pure ammonia for GC/CI-MS/MS and ICP-MS applications

Abstract

A method of supplying ammonia to a gas chromatography-chemical ionization tandem mass spectrometry (GC/CI-MS/MS) includes the steps of: providing ammonium carbonate and diethanolamine in a reaction vessel; heating the reaction vessel to a temperature of 50-60? C. to decompose the ammonium carbonate to form ammonia, carbon dioxide and water; absorbing the carbon dioxide and water by the diethanolamine to form diethanolamine carbonate; and supplying the ammonia to the GC/CI-MS/MS. Another method of supplying ammonia to a gas chromatography-chemical ionization tandem mass spectrometry (GC/CI-MS/MS) includes the steps of: providing ammonium carbonate and a mixture of monoethanolamine and diethanolamine in a reaction vessel; reacting the ammonium carbonate with the monoethanolamine to form ammonia and monoethanolamine carbonate; and supplying the ammonia to the GC/CI-MS/MS.

Claims

1. A method of supplying ammonia to a gas chromatography-chemical ionization tandem mass spectrometry (GC/CI-MS/MS) comprising the steps of: providing ammonium carbonate and a mixture of monoethanolamine and diethanolamine in a reaction vessel; reacting the ammonium carbonate with the monoethanolamine to form ammonia and monoethanolamine carbonate; and supplying the ammonia to the GC/CI-MS/MS.

2. The method according to claim 1 further comprising heating the monoethanolamine carbonate to release carbon dioxide and water, and regenerate the monoethanolamine.

3. The method according to claim 2, wherein the monoethanolamine carbonate is heated at 150? C. for 2 hours.

4. The method according to claim 1 wherein the ammonium carbonate and the mixture of monoethanolamine and diethanolamine are provided in the reaction vessel in a 1:2 weight ratio.

5. The method according to claim 1 wherein the mixture of monoethanolamine and diethanolamine comprises 50% by weight monoethanolamine and 50% by weight diethanolamine.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 shows the elements and functions of the ammonia-generating device.

(2) FIG. 2 shows GC-MS/MS chromatograms for the analysis of 24 drugs using methane and ammonia as reagent gas. As presented in the figure, the responses by ammonia are approximately seven to ten times that of methane.

(3) FIG. 3 shows GC-MS/MS chromatograms for the analysis of 10 ug/ml of 24 drugs using an ammonia gas cylinder and the ammonia-generating device using 1 ml/min ammonia as reagent gas. As presented in the chromatograms the response by the present ammonia-generating device is the same as the ammonia gas cylinder.

(4) FIG. 4 shows GC-MS/MS chromatograms for the analysis of blank (methanol) by ammonia gas cylinder and the ammonia-generating device. As shown in the chromatogram, the background noise generated by the ammonia gas cylinder is the same as a present ammonia-generating device.

(5) FIGS. 5A and 5B show the mass spectra for cocaine (FIG. 5A) and codeine (FIG. 5B) generated by the ammonia gas cylinder and the ammonia-generating device.

(6) FIG. 6 shows GC-MS/MS chromatograms for the repeated analysis of 10 ug/ml of 25 drugs using the present ammonia-generating device.

(7) Similar reference characters denote corresponding features consistently throughout the attached drawings.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

(8) The present invention provides a solution to the safety challenge of using a compressed ammonia gas cylinder with GC/CI-MS/MS and ICP-MS.

(9) In particular, the present subject matter relates to a method and device for safety generating of pure ammonia by reaction the ammonium carbonate with monoethanolamine (MEA) and diethanolamine (DEA) in a stainless-steel reaction vessel connected to a heating control device.

(10) The generation of pure ammonia gas is based on two methods: (1) thermal decomposition of ammonium carbonate to ammonia, carbon dioxide, and water (2:1:1), and then absorbing of CO.sub.2 and H.sub.2O by DEA; and (2) direct reaction of ammonium carbonate (less stable form) with MEA to form ammonia gas and MEA carbonates (more stable form). In addition, the present contemplates recycling/regenerating of MEA and DEA for another batch of ammonia production by heating their carbonate/carbamate derivatives at 150? C. for 2 hours.

(11) According to the present subject matter, the disclosed method and device provide at least two advantages, namely (a) an average ammonia-releasing rate by controlling the temperature of the device, and (b) flowing other gases such as helium or nitrogen through the system to minimize the negative effects of a high concentration of ammonia on the vacuum pump fluids and seals of the GC-MS/MS. With respect to the development of the present subject matter, several parameters such as repeatability of the analysis, potential interferences of alkanolamines on the mass quality, and the ratio of water and oxygen after several injections of samples are studied to evaluate any negative effects of the present generating ammonia on GC-MS/MS performance or the analysis. Based on the results discussed below, the present generating ammonia device provides pure ammonia the same as the ammonia gas cylinder.

(12) Alkanolamines such as monoethanolamine (MEA) and diethanolamine (DEA) are used as CO.sub.2 capture in industrial processes. Specifically, alkanolamines are highly boiling points, very low vapor pressure, stable, non-flammable, cheap and safe to handle compounds. CO.sub.2 is typically absorbed by the amine function groups of alkanolamines to form carbonates (in the presence of H.sub.2O) or carbamates by Zwitterion mechanism. This reaction is reversible, and alkanolamines can be recycled by heating their carbonates at 130-150? C. to release CO.sub.2 and H.sub.2O.

(13) FIG. 1 depicts a set-up for a reaction vessel capable of generating pure ammonia to be supplied to GC/CI-MS/MS and ICP-MS. In particular, reaction vessel 10 has a body 16 which forms a reservoir that holds the various reactants. Body 16 can be made of any suitable material, including stainless steel in a non-limiting example. A lower portion of body 16 is positioned on a heating element 12. Heating element 12 is utilized to maintain the temperature of the elements found in the reservoir. In a non-limiting example, heating element 12 is a hot plate that allows for temperature control of the reactants.

(14) Loaded into the bottom of the reservoir of the body 16 is a powder 14 of ammonium carbonate (NH.sub.4).sub.2CO.sub.3. A reaction liquid 18 is then loaded into the reaction vessel. Following loading of the reaction liquid 18, a filter 28 is positioned in an upper part of body 16, followed by attaching a cap 20 to seal the reaction vessel. The cap 20 is the same material as the body 16. In an embodiment, the filter 28 is a cellulose filter and the cap 20 is made of stainless steel. The filter 28 is positioned to keep any material other than ammonia from exiting reaction vessel 10. Three connections 22, 24, 26 are located in cap 20. One connection 22 connects the reaction vessel to the GC/CI-MS/MS and ICP-MS. A second connection 24 is a fitting for connecting nitrogen or helium gas to the reaction vessel. A third connection 26 is a connection fitting for connecting a pressure gauge to monitor the pressure of the ammonia gas generated in reaction vessel 10.

(15) In an embodiment, reaction liquid 18 is DEA. In this embodiment, the ammonium carbonate and the reaction liquid are added in a 1:2 weight ratio. While this embodiment discloses a 1:2 weight ratio of ammonium carbonate to reaction liquid, other weight ratios are also contemplated as being within the scope of this disclosure. Other ammonium carbonate to reaction liquid weight ratios contemplated include, without limitation; 1:1; 1:1.5; 1:2; 1:2.5; and 1:3.

(16) In another embodiment, reaction liquid 18 is a mixture of MEA and DEA. In this embodiment, the ammonium carbonate and the reaction liquid are added in a 1:2 weight ratio, and the weight ratio of MEA to DEA is 1:1, resulting in an overall weight ratio of ammonium carbonate to MEA to DEA is 1:1:1. While this embodiment discloses a 1:2 weight ratio of ammonium carbonate to reaction liquid, other weight ratios are also contemplated as being within the scope of this disclosure. Other ammonium carbonate to reaction liquid weight ratios contemplated include, without limitation, 1:0.5; 1:1; 1:1.5; 1:2; 1:2.5; and 1:3. Likewise, other weight ratios of MEA to DEA are also contemplated, including non-limiting examples of 0.5:1; 0.75:1; 1:0.75; and 1:0.5.

(17) The present subject matter employs the reaction vessel described above to generate pure ammonia to be fed to the GC/CI-MS/MS and ICP-MS. The method of generating pure ammonia is based on one of two chemical reactions: (1) thermal decomposition of ammonium carbonate to 2NH.sub.3, CO.sub.2, and H.sub.2O, and absorbing CO.sub.2, and H.sub.2O by DEA; or (2) replacement of ammonia by alkylamino group of MEA, and DEA to form more stable carbonates. Alkyl amines have stronger basicity than ammonia, because the electron donating inductive effect of the alkyl groups (NHCH.sub.2CH.sub.2) increases the electron density around the nitrogen, thereby, nucleophilic substitution of ammonium by amine group to form a more stable anionic salt. In accordance with the present subject matter, MEA and DEA can be recycled/regenerated for other batches of ammonia by heating their carbonate derivatives at 150? C. for 2 hours. One more advantage of this method is visually monitoring the method, whereas carbonate salt of MEA and DEA is very soluble in both chemicals (due to MEA and DEA having hydroxy groups abilities to dissolve carbonate salt) that makes the method easy to monitor the quantity of ammonium carbonate, whereas ammonium carbonate is not soluble in MEA and DEA.

(18) One reaction mechanism to generate the pure ammonia is by thermal decomposition. This mechanism follows as:
(NH.sub.4).sub.2CO.sub.3+Heating.fwdarw.2NH.sub.3(gas)+CO.sub.2(gas)+H.sub.2O
DEA+2NH.sub.3(gas)+CO.sub.2(gas)+H.sub.2O.fwdarw.2NH.sub.3(gas)+DEA carbonate(soluble in DEA)
The DEA can be regenerated or recycled by heating the DEA carbonate/carbamate according to: DEA carbonate/carbamate+Heating at 150? C..fwdarw.DEA+CO.sub.2+H.sub.2O.

(19) In this embodiment, due to DEA being very slow for interacting with the ammonium carbonate at ambient temperature, the generation of moderate ammonia is controlled by increasing the temperature. Using a temperature within a range of 40-60? C. increases the reaction rate and decomposes ammonium carbonate to ammonia, CO.sub.2, and H.sub.2O, with the carbon dioxide and water being absorbed by the DEA. The advantages of using DEA as an absorbing agent in this method are a very low vapor pressure (<1 Pa (at 20? C.)), a high boiling point (271.1? C.), and the method is generally inexpensive.

(20) In another embodiment, pure ammonia is generated by a replacement reaction according to:
MEA+(NH.sub.4).sub.2CO.sub.3RT.fwdarw.2NH.sub.3(gas)+MEA carbonate(soluble in MEA and DEA).

(21) As with the embodiment above, MEA can be regenerated/recycled by heating the MEA carbonate according to: MEA carbonate+Heating at 150? C..fwdarw.MEA+CO.sub.2+H.sub.2O

(22) In this embodiment, due to MEA interacting strongly with ammonium carbonate at ambient temperature, DEA is mixed with the MEA to slow the reaction rate and generate ammonia at an average rate (1-25 psi), based on MEA and DEA ratio, and amount of ammonium carbonate. It is noted that the reaction of MEA with ammonium carbonate was associated with dropping in the temperature of the medium (an endothermic reaction). The average ammonia-releasing rate can be controlled by increasing the temperature from 20-45? C. or changing the MEA and DEA ratio. It is noted that adding water drops during the regeneration process of MEA or DEA carbonate/carbamate increases the decomposition rate and therefore reduces the reaction period. It has been noted that using a stirrer tool inside the reservoir helps to release ammonia above the aqueous layer. In developing the present subject matter, other sources of ammonium were also tested in the above methods. Ammonium carbamate was tested as a source of ammonia. Pure ammonia is generated as same as ammonium carbonate. The advantage of using ammonium carabamate is that no H.sub.2O is formed, while the disadvantage is the ammonium carbamate is expensive compared to ammonium carbonate. Another ammonia-generating material such as ammonium chloride (NH.sub.4CL) was tested as a source of ammonia. MEA generates ammonia at room temperature, while DEA at 70? C. The disadvantage of using ammonium chloride is that the hydrochloride salt of alkanolamines cannot be recycled for future batches.

(23) An aspect of the present subject matter is that the pure ammonia generated by the above methods is fed to various analytical equipment. With respect to MS/MS, when in operation, the high vacuum of ions source and MS/MS help ammonia gas to enter the instrument with a constant flow rate because the MS/MS operates under a high vacuum and functions to control the flow rate of reagent gases. Furthermore, with respect to the development of the subject matter, several parameters such as repeatability of the analysis, potential interferences of DEA on the mass quality, and the ratio of water and oxygen after several injections of samples were studied to evaluate any negative effects of the present generating ammonia on GC-MS/MS performance or the analysis. The repeatability of the analysis was evaluated by running 150 samples in different three days. Potential interferences of DEA on the chromatogram or mass spectra were determined by analysis of solvent (methanol) and drug standards using an ammonia gas cylinder and using the presented generating-ammonia advice. GC-MS/MS performance has checked the ratio of water and oxygen before and after the analysis of 100 samples by the presented generating-ammonia advice. Based on the results, the present generating ammonia device provides pure ammonia the same as the ammonia gas cylinder.

(24) Particular results of various testing parameters are as shown in the following Figures;

(25) FIG. 2 shows overlapping chromatograms for the analysis of 10 ?g/ml of 24 drugs using ammonia generated from the above methods and methane as reagent gases. In particular, the chromatograms are for (1) amphetamine; (2) methamphetamine; (3) methcathinone; (4) methadrone; (5) 3,4-methulenedioxyamphetamine (MDA); (6) 2,3,4-methylenedioxymethamphetamine (MDMA); (7)3,4-methylenedioxyethylamphetamine (MDEA); (8) methedrone; (9) methylone; (10) caffeine; (11) phencyclidine (PCP); (12) 2,5-dimethoxy-4-methylphenethylamine (2C-D); (13) tramadol; (14) chlorpheniramine; (15) 3,4-methylene-?-pyrrolidinobutiophenone (MDPBP); (16) amitriptyline; (17) coca?ne; (18) desipramine; (19) naphyrone; (20) codeine; (21) diazepam; (22) nordiazepam; (23) oxycodone; and (24) 6-monoacetylmorphine (6-MAM).

(26) FIG. 3 shows GC-MS/MS chromatograms for the analysis of 10 ?g/ml of 24 drugs using ammonia from a typical gas cylinder and ammonia generated from the above methods as reagent gases. In particular, the chromatograms are for (1) amphetamine; (2) methamphetamine; (3) methcathinone; (4) methadrone; (5) 3,4-methulenedioxyamphetamine (MDA); (6) 2,3,4-methylenedioxymethamphetamine (MDMA); (7)3,4-methylenedioxyethylamphetamine (MDEA); (8) methedrone; (9) methylone; (10) caffeine; (11) phencyclidine (PCP); (12) 2,5-dimethoxy-4-methylphenethylamine (2C-D); (13) tramadol; (14) chlorpheniramine; (15) 3,4-methylene-?-pyrrolidinobutiophenone (MDPBP); (16) amitriptyline; (17) cocaine; (18) desipramine; (19) naphyrone; (20) codeine; (21) diazepam; (22) nordiazepam; (23) oxycodone; and (24) 6-monoacetylmorphine (6-MAM).

(27) FIG. 4 shows a chomatogram for the analysis of methanol (blank) with ammonia from the above methods and ammonia from a typical gas cylinder.

(28) FIG. 5A shows the mass spectra of coca?ne with ammonia from the above methods and ammonia from a typical gas cylinder.

(29) FIG. 5B shows the mass spectra of codeine with ammonia from the above methods and ammonia from a typical gas cylinder.

(30) FIG. 6 shows chromatograms for 20 repeated analyses of drug standards using ammonia generated by the above methods.

(31) As can be seen from FIGS. 2-6, the use of ammonia from the above methods mimics well with respect to standard ammonia sources. Thus, it is contemplated that the above methods generate ammonia sufficient for use in various analytical equipment.

(32) It is to be understood that the present subject matter is not limited to the specific embodiments described above, but encompasses any and all embodiments within the scope of the generic language of the following claims enabled by the embodiments described herein, or otherwise shown in the drawings or described above in terms sufficient to enable one of ordinary skill in the art to make and use the claimed subject matter.