title: Development, validation, and application of a fast and simple GC-MS method for determination of some therapeutic drugs relevant in emergency toxicology.
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.
authors.affiliation: Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Saarland, Homburg (Saar), Germany. markus.meyer@uks.eu
authors.forename: Markus R
authors.initials: MR
authors.lastname: Meyer
authors.forename: Jessica
authors.initials: J
authors.lastname: Welter
authors.forename: Armin A
authors.initials: AA
authors.lastname: Weber
authors.forename: Hans H
authors.initials: HH
authors.lastname: Maurer
mesh_terms: D000082:Acetaminophen / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D000927:Anticonvulsants / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D011041:Poisoning / Q000175:diagnosis*; D015203:Reproducibility of Results; D020156:Salicylic Acid / Q000737:chemistry*; D012680:Sensitivity and Specificity; D014116:Toxicology / Q000379:methods*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000927:Anticonvulsants; D000082:Acetaminophen; D020156:Salicylic Acid