Screening of stabilizers for LC-MS/MS analysis of clevidipine and its primary metabolite in dog whole blood

被引:10
作者
Cao, Peng [1 ]
Li, Gao [1 ,2 ]
Huang, Ling [1 ]
Zhao, Shouwei [1 ]
Hu, Yang [1 ]
Qin, Lixia [1 ]
Qiu, Lihui [1 ]
Zhu, Wenwen [1 ]
Si, Luqin [1 ,2 ]
Huang, Jiangeng [1 ,2 ]
机构
[1] Huazhong Univ Sci & Technol, Sch Pharm, Dept Pharmaceut, Tongji Med Coll, Wuhan 430030, Peoples R China
[2] Huazhong Univ Sci & Technol, Hubei Engn Res Ctr Novel Drug Delivery Syst, Wuhan 430030, Peoples R China
关键词
TANDEM MASS-SPECTROMETRY; ACTING CALCIUM-ANTAGONIST; LIQUID-CHROMATOGRAPHY; BIOLOGICAL MATRICES; REMIFENTANIL; PLASMA; PRESSURE; DRUG; RAT; PHARMACOKINETICS;
D O I
10.4155/bio.15.74
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Background: Clevidipine is an ester-containing antihypertensive agent that undergoes rapid hydrolysis in blood. A reliable stabilizer cocktail containing citric acid and ascorbic acid was established and the LC-MS/MS method was validated for simultaneous determination of clevidipine and its major metabolite in beagle dog whole blood. Results: The stabilizer could nearly completely inhibit the esterase activity. Both analytes were extracted from whole blood by toluene and detected by MS/MS in positive ESI mode. The linearity range was 0.1-100.0 ng/ml for clevidipine and 1.0-1000.0 ng/ml for the primary metabolite. Conclusion: The stabilizer cocktail was able to effectively suppress the activity of esterase in blood. The method was successfully applied to a PK study of clevidipine in beagle dogs.
引用
收藏
页码:1457 / 1469
页数:13
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