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Quantitative determination of total methamphetamine and active metabolites in rat tissue by liquid chromatography with tandem mass spectrometric detection

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Abstract

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.

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Authors and Affiliations

  1. College of Pharmacy, Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, 4301 West Markham Street #522-3, 72205, Little Rock, AR

    Howard Hendrickson

  2. Department of Pharmacology and Toxicology, College of Medicine, Little Rock, AR

    Elizabeth Laurenzana & S. Michael Owens

Authors
  1. Howard Hendrickson
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  2. Elizabeth Laurenzana
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  3. S. Michael Owens
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Correspondence to Howard Hendrickson.

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Published: November 22, 2006

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Hendrickson, H., Laurenzana, E. & Owens, S.M. Quantitative determination of total methamphetamine and active metabolites in rat tissue by liquid chromatography with tandem mass spectrometric detection. AAPS J 8, 80 (2006). https://doi.org/10.1208/aapsj080480

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  • DOI: https://doi.org/10.1208/aapsj080480

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