Validated LC-MS/MS method for the determination of cycloserine in human plasma: Application to pharmacokinetic studies

[Speaker] Phongpan Mokmued:1
[Co-author] Triporn Wattananat:2, Surakameth Mahasirimongkol:1, Katsushi Tokunaka:3
1:Department of Medical Sciences, Medical Genetic Center, Medical Life Science Institute, Thailand, 2:Department of Medical Sciences, Bureau of Drug and Narcotic, Thailand, 3:Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Japan

A simple and rapid liquid chromatography tandem mass spectrometric method is developed and validated for the determination of cycloserine in human plasma. Carbamazepine is used as an internal standard. The method utilizes protein precipitation with acetonitrile followed by dilution with 50% methanol. The analyte and internal standard were chromatographed on an Acclaim 120 C18 (100 mm x 2.1 mm 3 um) column using methanol and 0.1% formic acid (70:30 v/v) as mobile phase. Detection was performed on a quadrupole mass spectrometer using an electrospray ionization interface in selected reaction monitoring mode. The method proves to be specific sensitive accurate precise and linear over the concentration range of 0.3-70 ug/ml with correlation coefficients greater than 0.995. The lower limit of quantification for cycloserine is 0.3 ug/ml using a 100-ul plasma sample. Intra- and inter-day precisions are less than 8.3% whereas accuracies are within 8.8%. The method is successfully applied to pharmacokinetic studies of cycloserine in 11 healthy Thai volunteers after oral administration of single dose of cyclosrine at 250 and 750 mg and multiple dose at 750 mg under fasting conditions.
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