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Research Article

Tissues Distribution of R-(−)- and S-(+)-m-Nisoldipine after Single Enantiomer Administration in Rats

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Pages 65-72 | Published online: 01 Jan 2009
 

Abstract

Rapid, sensitive, and selective high-performance liquid chromatography methods were developed and validated for determination of m-nisoldipine enantiomers in rat tissues. All of the samples were prepared based on a simple and efficient liquid–liquid extraction method. After validating that no racemation occurred by ULTRON ES-OVM (Japan), m-nisoldipine enantiomers were determined, respectively, on a reverse-phase C18 column (5 μm, 250 × 4.6 mm). This method was applied to study tissue distribution of m-nisoldipine enantiomers in rats after a single administration of m-nisoldipine enantiomers. By the two-sample t test, there were basically no significant differences between the two enantiomers in each tissue ( p > .05), which indicates that they may have the same potency in rats. In small intestine, lung, liver, and spleen, the concentrations of R-(–)- and S-(+)-m-nisoldipine were high at 30 and 150 min than that at 90 min, which showed that m-nisoldipine enantiomers may have the phenomenon of hepatoenteral circulation. A small quantity of the prototype of R-(–)- and S-(+)-m-nisoldipine in brain showed that they can cross the blood–brain barrier to arrive at the brain tissue. The high quantity of distribution in lung and brain implied that the lipophilicity of the drug was powerful.

ACKNOWLEDGMENTS

This project received financial support from the Research Project of Science and Technology of Hebei Province (06276407D).

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