Ovomucoid固定化3 μmキラルカラムを用いるジルチアゼム原薬および製剤中の光学異性不純物と類縁物質の迅速同時定量

Abstract

This paper describes the development of a rapid simultaneous HPLC evaluation method of related substances and optical purity of diltiazem (cis-(+)-(2S, 3S) form) and its formulations by employing a 3 mm ovomucoid conjugated chiral column. After optimization of the mobile phase, changing organic solvent species and its concentration, buffer species and concentration, buffer pH etc., successful simultaneous determination of its deacetyl form (diltiazem main impurity and degradation product) and a minor enantiomer (cis-(-)-(2R, 3R) form) was achieved within 2.5 min. The mobile phase used was a mixture of acetonitrile and 0.02 mol L -1 ammonium acetate buffer (pH 6.0) (12.5 : 87.5). By employing the developed HPLC method with a 3 mm ovomucoid column, no minor enantiomer and 0.1 % -0.4 % deacetyl form were found in all diltiazem drug substances, its tablets and injections (freezedried formulations) (cis-(+)-(2S, 3S) form), and they were stored at a room temperature for more than 10 years, showing diltiazem and its formulations are very stable pharmaceuticals.