Simultaneous determination of a novel diphenylpiperazine calcium channel blocker and its four metabolites in rat liver microsomes by liquid chromatography tandem mass spectrometry.
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| Abstract |
Dipfluzine hydrochloride (Dip), a novel diphenylpiperazine calcium channel blocker, has revealed the characteristics of a promising candidate for the treatment of cerebral vascular diseases in preclinical studies. Our research identified and quantified Dip and its 4 metabolites (M1, M2, M4 and M5) in rat liver microsomes by liquid chromatography tandem mass spectrometry. The results showed that Dip was firstly metabolized to M1 and M5 by 1- and 4-dealkylation from a piperazine nitrogen, and then the latter was subsequently metabolized to M2 and M4. The concentrations of Dip, M1, M2 and M5 were 557.3 ± 26.3, 854.3 ± 46.0, 2796.7± 126.9, 2473.3 ± 82.6 and 4.0 ± 0.4, 2.4 ± 0.1, 318.2 ± 8.7 and 27.4 ± 1.5 ng/ml in male and female rats, respectively. M4 (404.2 ± 22.2 ng/ml) was detected only in males not in females, suggesting that there is gender difference in the metabolism of Dip.
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| Authors | Wei Guo, Dezhi Kong, Yingfeng Du, Xiaowei Shi, Wei Wang, Yongli Wang |
| Journal | Pharmacology (Pharmacology) Vol. 89 Issue 3-4 Pg. 201-10 ( 2012) ISSN: 1423-0313 [Electronic] Switzerland |
| PMID | 22473133 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study) |
| Copyright | Copyright © 2012 S. Karger AG, Basel. |
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