Simultaneous assay of four stereoisomers of diltiazem hydrochloride. Application to in vitro chiral inversion studies |
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Authors: | K Ishii K Minato H Nakai T Sato |
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Institution: | (1) Analytical Research Laboratory, Tanabe Seiyaku Co., Ltd., 16-89, Kashima 3-chome, Yodogawa-ku, 532 Osaka, Japan |
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Abstract: | Summary The simultaneous stereospecific assay of four stereoisomers of diltiazem hydrochloride in bulk drug and aqueous solution was
developed using HPLC on a Chiralcel OF column. The four isomers were quantitated with good precision by the internal standard
method. The chiral inversion of (+)-cis-diltiazem hydrochloride in vitro, stability of its (2S, 3S) configuration in the solid
and aqueous states was examined by HPLC. Chiral inversion of (+)-cis-diltiazem hydrochloride was not observed in the solid
state, and its (2S, 3S) configuration was stable to heat, humidity and light. Chiral inversion of (+)-cis-diltiazem hydrochloride
(2S, 3S) was observed in aqueous solution under UV, but not in aqueous solution stored at 80°C for 5 h nor under visible light
for 10 h. The (+)-cis-diltiazem hydrochloride (2S, 3S) epimerized to (+)-trans-diltiazem hydrochloride (2R, 3S) with a half-life
of 5 h in aqueous solution under UV but the reverse chiral inversion of (+)-trans-diltiazem hydrochloride (2R, 3S) to (+)-cis-diltiazem
hydrochloride (2S, 3S) was not observed. |
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Keywords: | Column liquid chromatography Diltiazem hydrochloride stereoisomers Chiralcel OF Chiral inversion Epimerization |
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