Determination of dehydroandrographolide succinate in human plasma by liquid chromatography tandem mass spectrometry (LC-MS/MS): Method development, validation and clinical pharmacokinetic study.
A LC-MS/MS method was developed and validated for the determination of dehydroandrographolide succinate (DAS), a traditional Chinese medicine derivative used for the treatment of pneumonia, upper respiratory tract infection, and chronic bronchitis. Following protein precipitation, DAS was detected by ion transition at m/z 531.2/99.0 in multiple reaction monitoring mode with negative electrospray ionization-tandem mass spectrometry. The limit of detection was 0.5ng/mL, and the lower limit of quantification was 10ng/mL in human plasma. Good linearity was maintained over the range of 10-5000ng/mL, and the correlation coefficient was better than 0.99. The accuracy ranged from 95.3% to 113%, RSD from 0.928% to 6.47%, for the within- and between-run analysis at all QC levels. The recovery ranged from 85.5% to 93.4% and the matrix effect from 107% to 119%. No significant carryover and good stability were found during method validation. The developed method was successfully applied to the determination of DAS in human plasma in a pharmacokinetic study following intravenous infusion of potassium sodium DAS to nine healthy volunteers.
Li
Shuijun
S
Central Laboratory, Shanghai Xuhui Central Hospital, 966 Huaihai Middle Road, Shanghai 200031, China. lishuijun@gmail.com
Yang
Ding
D
Zhang
Mengqi
M
Zhou
Juzhen
J
Li
Rui
R
Lu
Chuan
C
Liu
Yun
Y
Liu
Yanmei
Y
Wang
Yiping
Y
Yu
Chen
C
D000328:Adult; D016009:Chi-Square Distribution; D002853:Chromatography, Liquid / Q000379:methods*; D004224:Diterpenes / Q000097:blood* / Q000493:pharmacokinetics; D004355:Drug Stability; D004365:Drugs, Chinese Herbal; D005260:Female; D006801:Humans; D008297:Male; D015203:Reproducibility of Results; D013386:Succinates / Q000097:blood* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*
D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D013386:Succinates; C478098:dehydroandrographolide