Rapid Gas Chromatography-mass Spectrometry Method Research Articles

Development and validation of a rapid GC–MS method for seized drug screening

Controlled substances are one of the most commonly analyzed types of evidence in forensic laboratories. Persistent, high levels of case submissions in recent years have created a need for rapid screening techniques to decrease case backlogs and expedite confirmatory analyses. The most utilized technique for the analysis of seized drugs is gas chromatography mass spectrometry (GC-MS). While this approach typically takes tens of minutes, advances in the technique have enabled approximately 1 min run times with a short column and a rapid (10’s °C/s) temperature program. These advances were used in this work to develop and validate a rapid GC-MS method for screening seized drug samples. Method validation was completed to determine retention time repeatability and reproducibility, limits of detection, identification accuracy, selectivity, and carryover. Validation results showed the utility of this method for accurate and precise qualitative analyses for the screening of seized drugs across seven different drug classes. The optimized method was then applied to 15 real and mock case samples from the Maryland State Police Forensic Sciences Division. Controlled substances, cutting agents, and other diluents were identified from these samples using acceptance criteria of retention time and mass spectral comparisons currently used in casework. Using rapid GC-MS methods in casework could enable faster and more reliable presumptive testing results for the analysis of seized drug exhibits.

Chemical profile, acetylcholinesterase, butyrylcholinesterase, and prolyl oligopeptidase inhibitory activity of Glaucium corniculatum subsp. refractum

Papaveraceae is one of the prominent alkaloid-containing families, and plants of the genus Glaucium (Papaveraceae) are known for their bioactive alkaloids. Glaucium species have been used in traditional medicine in Turkey as an analgesic, narcotic, sedative, and antitussive. In this study, it was planned to evaluate the inhibitory activity of an alkaloidal extract of Glaucium corniculatum subsp. refractum on acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and prolyl oligopeptidase (POP), as well as exploring the chemical profile of the plant by using Gas Chromatography-Mass Spectrometry (GC-MS). The AChE, BuChE and POP inhibition activities of the alkaloidal extract of G. corniculatum subsp. refractum were determined spectrophotometrically. A rapid GC-MS method was used to identify alkaloids that could be responsible for these inhibition activities. In total, eleven alkaloids were identified in the alkaloid extract of the plant by GC-MS. Allocyptopine (52.92%) and protopine (25.38%) were found as the major constituents. The alkaloidal extract of G. corniculatum subsp. refractum showed potent AChE inhibitory activity (IC50:1.25 µg/mL) and BuChE inhibitory activity (IC50: 7.02 µg/mL). The extract also showed a remarkable inhibitory effect on POP with an IC50 value of 123.69 µg/mL. This study presents the first GC-MS investigation and POP inhibitory activity of G. corniculatum subsp. refractum.

Determination of alkyl methanesulfonates in doxazosin mesylate by gas chromatography-mass spectrometer

High sensitive rapid gas chromatography-mass spectrometry method for the determination of four carcinogenic alkyl methanesulfonates viz. methyl methanesulfonate, ethyl methanesulfonate, isopropyl methanesulfonate and n-butyl methanesulfonate in doxazosin mesylate has been presented by using selective ion monitoring mode. The optimum separation was achieved between methyl methanesulfonate, ethyl methanesulfonate, isopropyl methanesulfonate and n-butyl methanesulfonate on a DB-5 (30 m×0.32 mm×1.0 μm) capillary column under programming temperature. Acetonitrile, water and ammonia (90:9:1 v/v/v) mixture was used as diluent. Various factors involved in the gas chromatography-mass spectrometry method development are also presented. This method was validated as per International Conference on Harmonization guidelines. The limit of quantitation of methyl methanesulfonate, ethyl methanesulfonate, isopropyl methanesulfonate and n-butyl methanesulfonate is 6 ppm with respect to 30 mg/ml of doxazosin mesylate.

Urinary γ-Hydroxybutyrate Concentrations in 1126 Female Subjects

γ-Hydroxybutyrate (GHB) and its metabolic precursor γ-butyrolactone (GBL) are often implicated in cases of drug-facilitated sexual assault (DFSA), although definitive confirmation of GHB/GBL ingestion is complicated by GHB's endogenous nature and rapid elimination following ingestion. Multiple studies have attempted to establish a discriminant limit (generally 10 mg/L) above which urinary GHB concentrations can be considered consistent with GHB/GBL consumption. To supplement the currently available data, a rapid gas chromatography-mass spectrometry method was developed and validated for the analysis of GHB (following acidic conversion to GBL) and used to analyze urine samples collected from 1126 women (mean = 0.84 mg/L, median = 0.68 mg/L, range = 0.00-5.5 mg/L). GHB concentrations were shown to be independent of urinary pH (within the range 4.6-9.3), age (within the range 18-35 years), body mass index (within the range 13.8-36.3), and race. Adjusting GHB concentrations with respect to urinary specific gravity had little effect on the mean value (0.91 mg/L) and range (0.0-7.76 mg/L), although a statistically significant trend of increasing GHB concentration with specific gravity could be observed. Our results can be taken to offer further support for the 10 mg/L discriminant limit for GHB administration in antemortem urine samples.

A rapid gas chromatography–mass spectrometry method for quantification of alkylresorcinols in human plasma

Alkylresorcinols (ARs) are phenolic lipids that among foods are found almost exclusively in whole grain and bran products based on wheat and rye. They have been suggested to be used as selective biomarkers of whole grain wheat and rye intake and, thus, may serve as an alternative/complement to commonly used dietary assessment methods in epidemiological studies. For such investigations where analysis of large numbers of valuable samples is required, rapid, sensitive, and repeatable methods are essential. In this article, we describe a rapid and sensitive gas chromatography–mass spectrometry (GC–MS) method for quantification of AR homologues C17:0, C19:0, C21:0, C23:0, and C25:0 in human plasma. The method uses Oasis MAX solid phase extraction cartridges for sample cleanup. A plasma sample of 0.2 ml could be used without preincubation with water. Samples in the range of 7 to 8750 nmol total AR/L were successfully analyzed with the method described, and the average total AR recovery within the reported range was 92 ± 12%. The within- and between-day precision values of total AR concentration in a quality control sample, determined as the coefficients of variation, were on average 7 and 10%, respectively. Approximately 30 to 50 samples could be analyzed within 1 day. The improved GC–MS method presented can be used for rapid analysis of ARs in relatively small sample volumes.

Development and Validation of a GC–MS Method for the Determination of Methyl and Ethyl Camphorsulfonates in Esomeprazole Magnesium

A rapid gas chromatography–mass spectrometry method for the identification and determination of two carcinogenic impurities viz. methyl camphorsulfonate (MCS) and ethyl camphorsulfonate (ECS) in esomeprazole magnesium (EOM) is developed for the first time. The factors affecting method development and the fragmentation patterns of MCS and ECS based on the mass spectral analysis are described. The limit of detection and limit of quantitation values for both compounds were established as 3 and 10 ppm, respectively with respect to 50 mg mL−1 of EOM. The method is linear within the range of 10–120 ppm and found to be precise, accurate, specific and robust.

The development and application of a rapid gas chromatography–mass spectrometry method to monitor buprenorphine withdrawal protocols

There are several drug therapies that can be used to treat opiate abuse. One such treatment that is currently gaining wide acceptance is the use of the combined agonist/antagonist drug buprenorphine. As with all long-term treatments, there is a potential for compliance issues to arise, which establishes the need for a technique to facilitate the monitoring of individuals prescribed buprenorphine. One such method has been developed and applied to the routine monitoring of buprenorphine and its primary metabolite in urine. The method was found to be sensitive (limits of detection of 1.0 ng/mL for both buprenorphine and norbuprenorphine), reproducible and linear up to 2000 ng/mL. This article describes the application of this method to the analysis of specimens collected from subjects prescribed a reducing low-dose buprenorphine regimen (10.0–0.4 mg per day) for acute opiate detoxification. A significant relationship between the daily dose and the mean creatinine-corrected concentration of buprenorphine in the urine was observed, together with a relatively stable relationship between the ratio of the urinary concentrations of norbuprenorphine to buprenorphine across the dose range studied.

Screening urine of 3-week-old newborns: transient methylmalonic and hydroxyphenyllactic aciduria.

Urinary methylmalonic acid (MMA) and 4-hydroxyphenyllactic acid (HPL) have been determined in 3345 and 2498 3-week-old newborns, respectively. Urine was collected onto filter paper and assayed by a rapid gas chromatography-mass spectrometry method. Forty-six infants (1.7%) had elevated MMA levels (greater than 58.5 micrograms/mg creatinine, means + 5 SD) and 31 infants (1.2%) had elevated levels of HPL (greater than 87.7 micrograms/mg creatinine, means + 5 SD). Fifteen infants with elevated values of MMA were retested from one to several months after the first test. In 12 infants the MMA levels normalized, while in the remaining three, elevated methylmalonic acid persisted. Nine infants with elevated values of HPL were retested, and in all except one, HPL levels normalized. No access to clinical evaluation of the infants was available. Transient methylmalonic aciduria and transient tyrosyluria affect a substantial number of infants and the clinical significance of this phenomenon has yet to be determined.

Gas chromatography-mass spectrometry determination of [ 15N]ammonia enrichment in blood and urine

A rapid gas chromatography-mass spectrometry method for [ 15N]ammonia analysis is deseribed which is based on the formation of [ 15N]glutamic acid from ammonia and analysis of isotopic abundance in the N-trifluoroacetyl- n-butylester glutamate derivative. Mean recovery of [ 15N]ammonia added to either plasma or urine was greater than 99% with a relative standard deviation of less than 10%. The method can be applied to the determination of extremely low levels of ammonia through an isotope dilution technique. The [ 15N]ammonia abundance of blood and urine was determined in an adult following on oral dose (500 mg) of 15NH 4Cl. A peak isotopic abundance of 13 atoms% excess was reached by 30 min. Urinary excretion of [ 15N]ammonia during the first 4 h after administration of the isotope amounted to 4.1% of the isotope administered.