Quantitative Determination of Total Methamphetamine and Active Metabolites in Rat Tissue by Liquid Chromatography With Tandem Mass Spectrometric Detection
Document Type
Article
Publication Date
11-22-2006
Description
High-throughput liquid chromatography with tandem mass spectrometric detection (LC-MS/MS) methodology for the determination of methamphetamine (METH), amphetamine (AMP), 4-hydroxymethamphetamine (4-OH-METH), and 4-hydroxyamphetamine (4-OH-AMP) was developed and validated using simple trichloroacetic acid sample treatment. The method was validated in rat serum, brain, and testis. Lower limits-of-quantitation (LOQ) for METH and AMP were 1 ng·mL-1 using positive ion electrospray tandem mass spectrometry (MS/MS). The accuracy of the method was within 25% of the actual values over a wide range of analyte concentrations. The within-assay precision was better than 12% (coefficient of variation). The method was linear over a wide dynamic range (0.3-1000 ng·mL-1). Quantitation was possible in all 3 matrices using only serum standards because of minimal matrix-associated ion effects or the use of an internal standard. Finally, the LC-MS/MS method was used to determine serum, brain, and testis METH and AMP concentrations during a subcutaneous infusion (5.6 mg kg-1 day-1) of METH in rats. Concentrations of 4-OH-AMP and 4-OH-METH were below the LOQ in experimental samples. The bias introduced by using serum calibrators for the determination of METH and AMP concentrations in testis and brain was less than 8% and insignificant relative to the interanimal variability.
Citation Information
Hendrickson, Howard; Laurenzana, Elizabeth; and Owens, S. Michael. 2006. Quantitative Determination of Total Methamphetamine and Active Metabolites in Rat Tissue by Liquid Chromatography With Tandem Mass Spectrometric Detection. AAPS Journal. Vol.8(4). https://doi.org/10.1208/aapsj080480 PMID: 17233534 ISSN: 1550-7416
