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2018 (v.26 no.3)

Translational and Clinical Pharmacology

Korean Society for Clinical Pharmacology and Therapeutics
ISSN: 2289-0882

  • Development of a UPLC-MS/MS method for the therapeutic monitoring of L-asparaginase

    Hyeon-Cheol Jeong, Therasa Kim, Deok-Hwan Yang, Kwang-Hee Shin

    TCP | v.26, no.3, pp.134-140, Sep, 2018


    This study aimed to develop a UPLC-MS/MS method for determining plasma levels of L-aspartic
    acid and L-asparagine and the activity of L-asparaginase. L-aspartic acid, L-asparagine, and L-aspartic
    acid-2,3,3-d3 were extracted from human plasma by protein precipitation with sulfosalicylic acid
    (30%, v/v). The plasma samples were analyzed using an Imtakt Intrada amino acid analysis column
    with 25 mM ammonium formate and 0.5% formic acid in acetonitrile as the mobile phase with step
    gradient method at a flow rate of 0.5 mL/min. The injection volume was 5 μL, and the total run time
    was 15 min. Inter- and intra-batch accuracies (%) ranged from 96.62?106.0% for L-aspartic acid
    and 89.85?104.8%, for L-asparagine, and the coefficient of variation (CV%) did not exceed 7%. The
    validation results for L-aspartic acid and L-asparagine satisfied the specified criterion, however, the
    results for L-asparaginase activity assay showed a borderline validity. This study could be a foundation
    for further development of therapeutic drug monitoring systems using UPLC-MS/MS.


    L-asparaginase, L-asparagine, L-aspartic acid, UPLC-MS/MS