HPLC-FLD method for simultaneous measurement of clevidipine butyrate and its metabolites
10.11665/j.issn.1000-5048.20150311
- VernacularTitle:HPLC-FLD法同时测定丁酸氯维地平及其代谢物
- Author:
Jinghong RONG
1
;
Yu LIU
;
Fang WANG
;
Yi LI
;
Degong YANG
;
Lijiang CHEN
Author Information
1. 辽宁大学药学院
- Publication Type:Journal Article
- Keywords:
clevidipine butyrate;
clevidipine acid;
lipid microspheres;
pharmacokinetics;
HPLC-FLD method
- From:
Journal of China Pharmaceutical University
2015;46(3):328-332
- CountryChina
- Language:Chinese
-
Abstract:
To evaluate pharmacokinetic and metabolic characteristics of clevidipine butyrate lipid microspheres(CDB-LM)injection in mice, a novel HPLC-FLD method was developed for simultaneous measurement of clevidipine butyrate(CDB)and its metabolites clevidipine acid(MI)in whole blood samples. The chromatographic column was Waters C18(4. 6 mm×150 mm, 5 μm)and the mobile phase is consisted of acetonitrile-methanol-phosphate(2 ∶1 ∶2). The detection wavelength of FLD included excitation wavelength at 358 nm and emission wavelength at 440 nm. The pharmacokinetic parameters of CDB and MI were calculated by using DAS 2. 0. Then obtained parameters were statisticaly analyzed using PASW Statistics 18. The results showed that the half-life of CDB and MI were about 4 min and 20 min, respectively. Pharmacokinetic parameters of the low- and high-dose groups were as follows: CL of CDB were 4. 21 and 2. 72 L ·min-1 ·kg-1; AUC0-t were 3. 86 and 6. 43 mg/L ·min; MRT0-t were 7. 09 and 6. 17 min. CL of MI were 0. 34 and 0. 22 L ·min-1 ·kg-1; AUC0-t were 52. 23 and 74. 90 mg/L ·min; MRT0-t were 201. 24 and 217. 33 min. A method of protein precipitation was established, and acetonitrile was used to deal with whole blood samples. This method was simple, fast, with no interference with endogenous impurities. The results showed that the established HPLC-FLD method was simple and sensitive. It can be used to determine CDB and MI simultaneously. Comparing the low-dose group with the high-dose group, it was found that the plasma concentration-time curve of the two groups revealed the same tendency, which confirms that CDB has a short half-life and that it metabolizes to MI quickly.