Determination of Isosorbide Mononitrate in Human Plasma by Gas Chromatography with Electron Capture Detector and Study on the Bioequivalence of Isosorbide Mononitrate Tablets

Objective:A gas chromatography with electron capture detector(GC-ECD) method was developed and validated to determine isosorbide mononitrate in plasma and evaluate the bioequivalence of two isosorbide mononitrate tablets(T and R).Methods:Isosorbide mononitrate was separated on a Dikma-17 column and was determined by GC-ECD method,and the internal standard was Nitroglycerin.A single oral dose of 40 mg isosorbide mononitrate was administered to 18 healthy volunteers in a randomized crossover study,and the pharmacokinetics and bioavailability were studied.Results:Isosorbide mononitrate was separated well with the endogenous substances,the calibration curve was linear in the range of 2.9～731.5 μg/L with r2=0.998,the absolute recovery was in the rang of 95.5%～112.9%(n=20),and the method recovery was in the rang of 90.1%～107.8%(n=15),inter-day RSD11.4%(n=15) and intra-day RSD11.7%(n=15).The AUC0→24 of the two tablets were(3642.5±731.4) and(3658.8±832.8) μg·h·L-1,Cmax were(477.5±65.0) and(474.2±77.6) μg/L,Tmax were(1.3±0.4) and(1.1±0.3) h.The relative bioavailability of tablets T was(100.8%±12.1%) when compared with tablets R.Conclusions:The established method is accurate and sensible for determination of isosorbide mononitrate in human plasma.Statistic analysis showed no significant difference between the two tablets,and bioequivalence was observed.