Drug testing in blood: validated negative-ion chemical ionization gas chromatographic-mass spectrometric assay for determination of amphetamine and methamphetamine enantiomers and its application to toxicology cases

Clin Chem. 2002 Sep;48(9):1472-85.

Abstract

Background: Enantioselective analysis of amphetamine (AM) or methamphetamine (MA) in urine is already a well-established tool for differentiation of illicit from therapeutic ingestion of AM or MA derivatives. However, because of the increasing importance of plasma or serum in analytical toxicology, a method for enantioselective analysis of AM and MA in these matrices is needed.

Methods: AM and/or MA were extracted from 0.2 mL of blood plasma or serum by mixed-mode solid-phase extraction. After derivatization with S-(-)-heptafluorobutyrylprolyl chloride, the resulting diastereomers were separated by gas chromatography on a HP-5MS column during a 15-min program and detected by mass spectrometry in the negative-ion chemical ionization mode (NICI-GC-MS). The method was fully validated and applied to >50 samples from authentic toxicology cases.

Results: The derivatized AM and MA enantiomers were well separated and sensitively detected. The method was linear from 5 to 250 micro g/L per enantiomer with analytical recoveries, accuracy, and within- and between-run precision well within required limits. Extraction yields were 88.9-98.6%. Implications of concentrations and enantiomeric composition of AM and MA in the authentic samples were considered.

Conclusions: This sensitive, reliable, rapid NICI-GC-MS assay is suitable for enantioselective determination of AM and MA in blood plasma or serum samples.

MeSH terms

  • Amphetamine / blood*
  • Amphetamine / chemistry
  • Blood Specimen Collection
  • Drug Stability
  • Fluorocarbons / chemical synthesis
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Indicators and Reagents
  • Methamphetamine / blood*
  • Methamphetamine / chemistry
  • Proline / analogs & derivatives
  • Proline / chemical synthesis
  • Sensitivity and Specificity
  • Stereoisomerism
  • Substance Abuse Detection / methods*

Substances

  • Fluorocarbons
  • Indicators and Reagents
  • Methamphetamine
  • N-heptafluorobutyrylproline
  • Proline
  • Amphetamine