Low pollutant dialysis solution

Abstract

A method for the determination of pollutants and leachables in a dialysis solution by stir bar sorptive extraction involves conditioning a sorptive material-coated stir bar, stirring the dialysis solution with the conditioned stir bar, desorbing of pollutants and leachables from the coated stir bar, and analyzing the desorbed pollutants and leachables by gas chromatography-mass spectrometry (GC-MS).

Claims

1. Method for determination of pollutants and leachables in a dialysis solution by stir bar sorptive extraction comprising the steps of conditioning a stir bar coated with a sorptive material by washing the coated stir bar in a mixture comprising methanol and dichloromethane, adding sodium chloride at a concentration of at least 90% saturation to the dialysis solution, stirring the dialysis solution with the conditioned coated stir bar, followed by desorption of pollutants and leachables from the coated stir bar, and analysis of the desorbed pollutants and leachables by gas chromatography-mass spectrometry (GC-MS).

2. Method of claim 1, wherein the conditioning step additionally comprises ultrasonic treatment.

3. Method of claim 1, wherein the sorptive material coating the stir bar is polydimethylsiloxane (PDMS).

Description

EXAMPLES

(1) The following 52 compounds were used as analytes:

(2) Phenol, 2-Hydroxyacetophenone, 2-tert-Butylphenol, 4-tert-butylphenol, 2,6-di-tert-butylphenol, 2,4-di-tert-butylphenol, bisphenol A (BPA), butylhydroxytoluene (BHT), cyclohexanol, 2-ethylhexanol, benzyl alcohol, dodecanol, octadecanol, diethyl-phthalate (DEP), di-isobutylphthalate, di-butylphthalate (DBP), dicyclohexylphthalate (DCHP), undecane, 2-(2-butoxyethoxy)ethyl acetate, methyl-iso-butylketone (MIBK), cyclohexanone, toluene, ethylbenzene, styrene, divinylbenzene (DVB), benzaldehyde, 1,2-dicyanobenzene and chlorobenzene, 4-tert-amylphenol, oleamide, erucamide and 1,4-diacetylbenzene, decanamide, dodecanamide, hexadecanamide, stearamide and 4-methyl-2-heptanone, tetradecanamide, 5,5-dimethyl-2,4-hexandione and 1,3-diacetylbenzene.

(3) The standard stock solution was prepared by dissolving these substances in ethanol with a final concentration of 3 mg/kg for each of the analytes.

(4) A second standard stock solution in ethanol was prepared for ten carboxylic acids with a concentration of about 6 mg/kg: 2-ethylhexanoic acid, heptanoic acid, octanoic acid, decanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, docosanoic acid and 3-(3,5-di-tert-butyl-4-hydroxyphenyl)-propionic acid.

(5) Both stock solutions were stored in the darkness at room temperature.

(6) A solution of phenanthrene-D.sub.10 (Sigma Aldrich) at 2 mg/kg in ethanol (p.a., Merck KGa) was used as an internal standard. All samples were spiked with this standard, to have a final concentration of 75 g/kg phenantrene-D.sub.10.

(7) The PDMS coated Twister stir bars were purchased from Gerstel GmbH (Mlheim, Germany). The stir bars were cleaned and conditioned before every measurement by stirring them in 6 mL of a 50:50 mixture of methanol and dichloromethane for 4 hours, with a renewal of the solvents after 2 hours. Afterwards, the stir bars were dried under pure nitrogen at 30 C. for 30 min and then conditioned at 300 C. for 4 hours. The stir bars were allowed to cool down to room temperature for 4 hours under nitrogen. The heat conditioning procedure with the additional cool down to room temperature was repeated once more.

(8) One peritoneal dialysis solution was analyzed. The dialysis solution was supplied in dual-chamber 5 L bags. Prior to analysis the contents of both chambers were thoroughly mixed directly before the measurement as described in the respective instructions of use. Afterwards four samples with 25 mL were extracted as described in the following.

(9) A sample volume of 25 mL was placed in glass head space vials with a nominal volume of 25 mL. Then 8.5 g sodium chloride and 100 L of the phenantrene-D.sub.10 solution were added and 2 cm long PDMS stir bars with a 1 mm thick PDMS coating (=126 L PDMS phase volume) were placed into the vials. Subsequently the vials were sealed with a crimp cap. The extraction was performed for 4 h at a stirring speed of 1100 rpm at 25 C. Afterwards, the stir bars were removed with a magnetic stir bar retriever, rinsed with water and shortly purged with nitrogen to remove the water from the surface. Rinsing with water does not influence the analytes, because they are absorbed within the PDMS and are not located on the surface. Finally, the stir bars were transferred into a desorption tube and placed on the auto sampler tray. These desorption tubes were cleaned after every three measurements by rinsing them first with water and afterwards with acetone. Subsequently they were dried over night at 70 C.

(10) The entire stir bar handling was done with tweezers, to avoid possible contamination by direct contact.

(11) The phenanthrene-D.sub.10 was used to spike every sample and served therefore as a control compound to assure an accurate and error free sample extraction procedure. Deviations from the usually obtained target ion peak area for phenanthrene-D.sub.10 point to a probably not correct stirring process during extraction or to an advanced aging of the stir bar.

(12) The GC/MS measurements were performed using a GC 7890 system from Agilent equipped with a thermal desorption unit TDU (Gerstel) and a cold injection system CIS (Gerstel). Additionally a multipurpose autosampler MPS (Gerstel) was used to introduce the stir bars into the TDU. The desorption took place in solvent vent mode at 280 C. for 10 min. Helium 5.0 was used to transfer the analytes into the CIS where they were cryo-focused at 120 C. Finally the CIS was heated up to 280 C. at a speed of 12 C./s and the analytes were injected into the GC column. The helium carrier gas had a constant flow rate of 1 mL/min. The temperature program used for chromatographic separation involved a one minute waiting time at 50 C. after the injection. Afterwards the temperature was increased from 50 C. to 150 C. at a rate of 10 C./min, and then maintained at this level for 5.5 min before increasing the temperature further at a rate of 50 C./min rate to 300 C., and then maintaining the temperature at this level for 10 min. The ion source was held at a temperature of 270 C. The detector was an Agilent 5973 quadrupole mass spectrometer (MS) with an electron impact (EI) source and was used in scan mode. Mass-to-charge ratios (m/z) were recorded at values between 25 and 700. The column used was a Zebron (ZB-50) capillary column (length 30 m, diameter 0.25 mm, film thickness 0.50 m, stationary phase: 50% diphenyl polysiloxane, 50% dimethyl polysiloxane) purchased from Phenomenex (Aschaffenburg, Germany).

(13) The sample of the peritoneal dialysis solution exhibited a broad spectrum of leachables, which represented about 75% of the components used for the standard stock solutions. This finding proved the practical relevance of the standard solution composition. No unknown substances were detected in any of the solutions during the GC-MS analysis. Most of the leachables were found in concentrations between 1 g/kg and 10 g/kg. Some of the leachables (diethyl phthalate, dibutyl phthalate, oleamide and erucamide) were found to be in the range down to 0.1 g/kg. No dicyclohexylphthalate and no BPA were detected.