Development of a UPLC-MS/MS method for the therapeutic monitoring of L-asparaginase
10.12793/tcp.2018.26.3.134
- Author:
Hyeon Cheol JEONG
1
;
Therasa KIM
;
Deok Hwan YANG
;
Kwang Hee SHIN
Author Information
1. College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Korea. kshin@knu.ac.kr
- Publication Type:Original Article
- Keywords:
L-asparaginase;
L-asparagine;
L-aspartic acid;
UPLC-MS/MS
- MeSH:
Ammonium Compounds;
Asparagine;
Aspartic Acid;
Drug Monitoring;
Humans;
Methods;
Plasma
- From:Translational and Clinical Pharmacology
2018;26(3):134-140
- CountryRepublic of Korea
- Language:English
-
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-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.