An LC-MS/MS Method for the Determination of Cycloserine in Human Plasma: Application to Pharmacokinetic Study


  • Phongpan Mokmued Department of Medical Sciences, Ministry of Public Health, Thailand
  • Triporn Wattananat Department of Medical Sciences, Ministry of Public Health
  • Surakameth Mahasirimongkol Department of Medical Sciences, Ministry of Public Health, Thailand
  • Hideki Yanai Department of Clinical Laboratory, Fukujuji Hospital, Japan
  • Taisei Mushiroda Laboratory for Pharmacogenomics, RIKEN Center for Integrative Medical Sciences, Japan
  • Katsushi Tokunaga Department of Human Genetics, The University of Tokyo, Japan


Cycloserine, human plasma, LC-MS/MS, pharmacokinetics


A simple and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of cycloserine in human plasma. Carbamazepine was used as an internal standard. The method utilized protein precipitation with acetonitrile followed by dilution with 50% methanol. The separation was performed on a C18 column using methanol-0.1% formic acid (70:30, v/v) as the mobile phase. Detection was performed on a quadrupole mass spectrometer using an electrospray ionization interface in multiple reaction monitoring mode. The method was proven to be specific, sensitive, accurate, precise, and linear over the concentration range of 0.3-70 µg/mL with correlation coefficients greater than 0.995. The intra- and interday precisions and accuracies were within 10.7%. The method was successfully applied to a pharmacokinetic study of cycloserine following the oral administration of 250 and 750 mg cycloserine capsules in 11 healthy Thai volunteers under fasting conditions.


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