Improved Gas Chromatographic Determination of Diltiazem and Deacetyldiltiazem in Human Plasma

This study describes an improved, simple, and specific gas chromatographic method for the determination of diltiazem (I) and deacetyldiltiazem (II) in human plasma using loxapine (III) as an internal standard. After extraction at pH 7.5 with anhydrous ether-ethyl acetate (1:1), II was silylated with N-methyl-N-(trimethylsilyl)trifluoroacetamide. The gas chromatograph, equipped with an electron-capture detector, allowed measurements as low as 2 ng/mL for I and 3 ng/mL for II. Recoveries of III, I, and II were 95, 85, and 79%, respectively. There were no interferences with endogenous substances in plasma or with common cardiovascular drugs. This method was used to measure plasma concentrations of two patients who received 20mg iv of I. The areas under the curve for these two patients were 275 and 273 ng·h/mL, respectively. The apparent volumes of distribution were 493.6 and 288.6 L, and the elimination half-lives were 4.70 and 2.73h. No deacetyldiltiazem could be detected in the blood after the single-dose diltiazem administration.