NDLI: A simplified LC−MS/MS method for rapid determination of cycloserine in small-volume human plasma using protein precipitation coupled with dilution techniques to overcome matrix effects and its application to a pharmacokinetic study

Content Provider	Springer Nature Link
Author	Mao, Zhengsheng Wang, Xin Li, Bingxin Jin, Jing Xu, Ming Liu, Youping Di, Xin
Copyright Year	2017
Abstract	Matrix effects have been a major concern when developing LC−MS/MS methods for quantitative bioanalysis of cycloserine. Sample handling procedures including solid phase extraction or derivatization have been reported previously by researchers to overcome matrix effects of cycloserine. In the present study, the possibility of reducing matrix effects of cycloserine using protein precipitation coupled with dilution techniques was investigated. Plasma samples were pretreated by protein precipitation with methanol followed by a 40-fold dilution with methanol–water (50:50, v/v). The analyte and the internal standard (mildronate) were chromatographed on a Shim-pack XR-ODS (100 mm × 2.0 mm, 2.2 μm) column using methanol–0.01% formic acid (70:30, v/v) as mobile phase and detected by multiple reaction monitoring mode via positive electrospray ionization. The total run time was only 2 min per sample. The suppression of cycloserine response was reduced with the matrix effects ranging between 80.5 and 87.9%. A lower limit of quantification (LLOQ) of 0.300 μg/mL was achieved using only 10 μL of plasma. The intra- and inter-day precisions were less than 4.8% and the accuracy ranged from −2.6 to 6.6%. The method was successfully applied to a pharmacokinetic study of cycloserine in 30 healthy Chinese male subjects after oral administration of a single dose of cycloserine at 250, 500 and 750 mg under fasting conditions. The newly developed method is simpler, faster, cost-effective, and more robust than previously reported LC-MS/MS methods.
Starting Page	3025
Ending Page	3032
Page Count	8
File Format	PDF
ISSN	16182642
Journal	Analytical and Bioanalytical Chemistry
Volume Number	409
Issue Number	11
e-ISSN	16182650
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2017-02-21
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cycloserine Matrix effects LC–MS/MS Human plasma Pharmacokinetic study Analytical Chemistry Biochemistry Laboratory Medicine Characterization and Evaluation of Materials Food Science Monitoring/Environmental Analysis
Content Type	Text
Resource Type	Article
Subject	Analytical Chemistry Biochemistry

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