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

  • Jeong, Hyeon-Cheol (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Kim, Therasa (Department of Hematology, Chonnam National University Hwasun Hospital) ;
  • Yang, Deok-Hwan (Department of Hematology, Chonnam National University Hwasun Hospital) ;
  • Shin, Kwang-Hee (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University)
  • Received : 2018.06.06
  • Accepted : 2018.07.25
  • Published : 2018.09.15

Abstract

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-$d_3$ 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 $5{\mu}L$, 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.

Acknowledgement

Supported by : National Research Foundation (NRF)

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