Improving Ion Mass Ratio Performance at Low Concentrations in Methamphetamine GC-MS Assay through Internal Standard Selection

• Published in: Journal of analytical toxicology 1996-11, Vol.20 (7), p.592-595
• Main Authors: Urry, Francis M., Kushnir, Mark, Nelson, Gordon, McDowell, Mitzi, Jennison, Tom
• Format: Article
• Language: English
• Subjects: Abundance; Biological and medical sciences; Chromatography; Drug abuse; Drug toxicity and drugs side effects treatment; Gas chromatography; Gas Chromatography-Mass Spectrometry - methods; Gas Chromatography-Mass Spectrometry - standards; Ions; Mass spectroscopy; Medical sciences; Methamphetamine; Methamphetamine - analysis; Pharmacology. Drug treatments; Reference Standards; Reproducibility of Results; Toxicity: nervous system and muscle
• ISSN: 0146-4760; 1945-2403
• DOI: 10.1093/jat/20.7.592

In federally regulated drug testing, laboratories must identify and quantitate drugs and their breakdown products by gas chromatography-mass spectrometry (GC-MS) to a concentration that is at least 60% below the cutoff concentration for reconfirmation purposes. Use of methamphetamine-d5 as an internal standard in routine testing with derivatization by HFBA was found to contribute m/z 91 and 118 ions to the same ions from the nondeuterated methamphetamine in the specimen. This resulted in poor chromatography and occasionally caused the 91/254 and 118/254 ion mass ratios to exceed the +20% acceptance limit established in the calibration process at low concentrations. The analogues methamphetamine-d8 and -d11 were evaluated for contributions to the nondeuterated methamphetamine ion fragments. Methamphetamine-d8 produced m/z 91 and 118 ions, but in less abundance than methamphetamine-d5. Methampbetamine-d11 was found to produce little or no detectable m/z 91 or 118. Replacing methamphetamine-d5 with methamphetamine-d11 eliminates this problem and allows the assay to consistently produce ion mass ratios and acceptable chromatography sufficient for identifying and quantitating methamphetamine at 60% below the 500-ng/mL cutoff concentration.