A One-Step and Sensitive GC-MS Assay for Meprobamate Determination in Emergency Situations

Abstract

A rapid, sensitive, and ready-to-use gas chromatography-mass spectrometry method for meprobamate assay using carisoprodol as internal standard is described. The method involves extracting a 0.2-mL sample with chloroform, previously acidified with HCl 0.2N. For the quantitative analysis, we used selected-ion monitoring mode, selecting the ion m/z 144 for quantification of meprobamate and m/z 245 for carisoprodol. Excellent linearity was found between 0 and 200 mg/L plasma. The limit of detection was 0.58 mg/L, and the limit of quantification was 1.93 mg/L. A high reproducibility [intra-assay coefficient of variation (CV) range of 2.3-4.3% and interassay CV range of 5.5-12.3%] and accuracy (intra-assay range of 96.8-112.3% and interassay range of 85.5-99.3%) were observed. Recoveries were concentration-independent (87.0%, 76.2%, and 81.2% for 20, 75 and 150 mg/L, respectively). No interference from endogenous compounds, other metabolites of meprobamate, or frequently coadministered drugs was detected. This sensitive, simple assay for meprobamate in plasma, whole blood, and urine meets the current requirements for bioanalytical assays in overdose cases.

HPLC MS/MS method for quantification of meprobamate in human plasma: Application to 24/7 clinical toxicology

“…Most of these methods use CPG [5][6][7][8][9][10][11][12][13][14][15] or HPLC-UV [4]. All of them required solid or liquid phase extraction and some of them derivatization of meprobamate to enhance detection.…”

“…Several methods have been reported for the quantification of meprobamate in human plasma, high-performance liquid chromatography [4] and gas chromatography [5][6][7][8][9][10][11][12][13][14][15]. These methods present the following drawbacks: long analysis time and/or complex sample pre-treatment (derivatization, solid or liquid phase extraction).…”

Toxicology of Specific Substances

“…It has lost its significance, since more modern medicaments such as benzodiazepines or benzodiazepine-related drugs (z-drugs) show less side effects. Nevertheless, it is still in use and intoxications still occur (Charron et al 2005;Daval et al 2006). Typical symptoms of overdose include CNS depression, weakness, clonus and hyperreflexia, tachycardia, hypotension and respiratory depression.…”

A rapid quantitative method of carisoprodol and meprobamate by liquid chromatography–tandem mass spectrometry

“…It can be taken up to six times per day at dosages ranging from 200 to 400 mg [2,5,7]. Therapeutic dosages of meprobamate and carisoprodol (MEPCAR) 4 decrease human performance and adversely affect driving safety [2,4,7]. The concentration of meprobamate (800 mg) in whole blood after 1-2 h is 16 mg/L [8].…”