Summary
A direct HPLC separation method was developed for the determination of the enantiomers of racemic precursors to diltiazem (I) and its 8-chloro derivatives (II). The enantiomers were successfully separated on a chiral ovomucoid column using an aqueous-organic mobile phase (reversed-phase HPLC). The influence of the organic modifier and buffer pH on the retention and enantioselectivity was investigated. The chromatographic conditions chosen for the separation permitted complete resolution of the enantiomers of both the acid (Ib and IIb) and methyl ester precursors (Ia and IIa) within 20 min. The influence of sample load on retention times, theoretical plates numbers, peak heights and peak areas was also investigated. The peak areas showed a good linearity over the concentration range examined, although all the others were influenced significantly by the sample size. An optical antipode of the intermediate to be determined could be detected by the area-percentage method down to ca. 0.1%, together with the determination of its precursor, including its optical purity.
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References
E. J. Ariens, W. Soudijin, P. Timmermans (eds), “Stereochemistry and Biological Activity of Drugs”, Blackwell, 1983, pp. 11–32.
I.W. Wainer, D.E. Drayer (eds), “Drug Stereochemistry”, Marcel Dekker, New York and Basel, 1988, pp. 209–226.
R. Dappen, H. Arm, V.R. Meyer, J. Chromatogr.373, 1 (1986).
D. Armstrong, Anal. Chem.59, 84A (1987).
S. Allenmark, “Chiral Separation by HPLC”, Ellis Horwood, Chichester, 1989, pp. 286–311.
J. Hermansson, Trends Anal. Chem.8, 251 (1989).
T. Miwa, M. Ichikawa, M. Tsuno, T. Hattori, T. Miyakawa, M. Kayano, Y. Miyake, Chem. Pharm. Bull.35, 682 (1987).
T. Miwa, T. Miyakawa, M. Kayano, Y. Miyake, J. Chromatogr.408, 316 (1987).
J. Iredale, A.F. Aubry, I. Wainer, Chromatographia31, 329 (1991).
Instruction manual ULTRON ES-OVM, Shinwakako, Kyoto, Japan, 1989.
M. Chaffman, R.N. Brogden, Drugs29, 387 (1986).
K. Kikkawa, S. Murata, T. Nagao, Arzneim.-Forsch.38, 526 (1988).
S. Murata, K. Kikkawa, H. Yabana, T. Nagao, Arzneim.-Forsch.38, 521 (1988).
H. Narita, S. Murata, H. Yabana, K. Kikkawa, Y. Sugawara, Y. Arimoto, T. Nagao, Arzneim.-Forsch.38, 515 (1988).
H. Inoue, M. Konda, T. Hashiyama, H. Otsuka, K. Takahashi, M. Gaino, T. Date, K. Aoe, M. Takeda, S. Murata, H. Narita, T. Nagao, J. Med. Chem.34, 675 (1991).
K. Abe, H. Inoue, T. Nagao, Yakugaku Zasshi108, 716 (1988).
R. Shimizu, K. Ishii, N. Tsumagari, M. Tanigawa, M. Matsumoto, I.T. Harrison, J. Chromatogr.253, 101 (1982).
R. Shimizu, T. Kakimoto, K. Ishii, Y. Fujimoto, H. Nishi, N. Tsumagari, J. Chromatogr.357, 119 (1986).
K. Ishii, K. Banno, T. Miyamoto, T. Kakimoto, J. Chromatogr.564, 338 (1991).
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Nishi, H., Fujimura, N., Yamaguchi, H. et al. Direct enantiomeric separation of racemic precursors to diltiazem hydrochloride and clentiazem maleate by HPLC on a chiral ovomucoid column. Chromatographia 35, 305–310 (1993). https://doi.org/10.1007/BF02277515
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DOI: https://doi.org/10.1007/BF02277515