High performance liquid chromatographic method for the determination of cinepazide maleate and its application to a pharmacokinetic study in rats

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2014-04, Vol.957, p.105-109
• Main Authors: Zhao, Jinyi, Song, Ying, Wang, Hujun, Sun, Yuan, Liu, Meiyou, Lu, Chengtao, Li, Yan, Wang, Shan, Zhu, Xiaohe, Hai, Wenli, Wen, Aidong, Jia, Yanyan
• Format: Article
• Language: English
• Subjects: Animals; Bioavailability; Chromatography; Chromatography, High Pressure Liquid - methods; Cinepazide maleate; Drug Stability; Guidelines; HPLC; Limit of Detection; Linear Models; Linearity; Liquid-Liquid Extraction; Liquids; Maleates; Method of validation; Pharmacokinetic; Phosphates; Piperazines - blood; Piperazines - chemistry; Piperazines - pharmacokinetics; Rats; Rats, Sprague-Dawley; Reproducibility of Results
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2014.02.038

•We established HPLC method for the determination of cinepazide maleate in rat plasma firstly.•We showed the pharmacokinetic parameter of cinepazide maleate after intravenous administration firstly.•This HPLC method was reliable, sensitive and easy to implement.•Cinepazide maleate injection were absorbed and eliminated quickly in rat, and the pharmacokinetic showed dose-dependence profile.•Injection of cinepazide maleate can improve the bioavailability. A simple and reliable high performance liquid chromatographic (HPLC) method has been developed and validated to quantify cinepazide maleate, a calcium blocker, in rat plasma. Cinepazide maleate and Tinidazole (internal standard) have been extracted by a simple liquid–liquid extraction before injection into chromatographic system. Chromatographic separation was achieved on a reversed phase C18 column with a mobile phase consisted of a water mixture of 10mM potassium dihydrogen phosphate (pH=4.5):methanol (40:60, v/v), pumped at flow rate of 1.0mL/min, and detected at 303nm. The method exhibited a linear range of 0.12–120μg/mL in blank rat plasma, with the lower detection limit of 0.06μg/mL. The method was statistically validated for linearity, accuracy, precision, selectivity and stability following FDA guidelines. The intra- and inter-assay coefficients of variation did not exceed ±15% from the nominal concentration. The accuracy of cinepazide maleate was within ±15% of the theoretical value. The assay has been applied successfully in a pharmacokinetic study of cinepazide maleate after a single intravenous at three doses in rat. And cinepazide maleate injection can improve the bioavailability of cinepazide maleate greatly, and has a dose-dependence profile in rats.