Development, validation, and application of a fast and simple GC-MS method for determination of some therapeutic drugs relevant in emergency toxicology

Ther Drug Monit. 2011 Oct;33(5):649-53. doi: 10.1097/FTD.0b013e3182305409.

Abstract

Background: To date, immunoassays are commercially available for quantification of valproic acid, salicylic acid, paracetamol, phenobarbital, phenytoin, and primidone. As they are no longer available, a fast, simple, and cost-effective quantitative gas chromatography-mass spectrometry (GC-MS) method was developed and fully validated for these drugs.

Methods: After simple and fast liquid-liquid extraction, the samples were analyzed by GC-MS using the selected ion monitoring mode. The method was validated including the parameters selectivity, calibration model, precision, accuracy, and extraction efficiency.

Results: The above-mentioned analytes were separated within 8.5 minutes and sensitively detected. No interfering peaks were observed in blank samples from 8 different sources. The linearity ranges were 20-200 mg/L for valproic acid, 100-1200 mg/L for salicylic acid, 10-200 mg/L for paracetamol, 10-200 mg/L for phenobarbital, 4-20 mg/L for primidone, and 2.5-30 mg/L for phenytoin. Generally accepted criteria for accuracy and precision were fulfilled for all analytes using 6-point calibration. Even 1-point calibration was applicable for all analytes. The assay was successfully applied to analysis of real plasma samples and proficiency testing material.

Conclusions: The assay described allowed fast and reliable determination of analytes relevant in the diagnosis of poisonings. Furthermore, time- and cost-saving 1-point calibration was shown to be suitable for daily routine work, especially in emergency cases.

MeSH terms

  • Acetaminophen / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anticonvulsants / chemistry
  • Gas Chromatography-Mass Spectrometry / methods*
  • Humans
  • Poisoning / diagnosis*
  • Reproducibility of Results
  • Salicylic Acid / chemistry*
  • Sensitivity and Specificity
  • Toxicology / methods*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Anticonvulsants
  • Acetaminophen
  • Salicylic Acid