以液相層析法同時分析製劑中 Verapamil 與 Trandolapril   全文下載

Development and Validation of a Liquid Chromatographic Method for Concurrent Assay of Weakly Basic Drug Verapamil and Amphoteric Drug Trandolapril in Pharmaceutical Formulations

以逆向液相層析法分析弱鹼藥物verapamil仍有問題，特別是當這些藥物與其他兩性化合物像trandolapril併用的時候。在本研究中，發展出一簡單、精確且完全驗證的RP-LC方法，用於同時檢測verapamil與trandolapril合併使用的劑型。LC方法對於verapamil與trandolapril的定量範圍，分別在0.50-18.00及0.05-1.00 μg/mL，偵測極限值則分別為0.008及0.018 μg/mL。此外，滯留係數依離子性物質受移動相的PH值影響，進而測定verapamil與trandolapril的pKa值。為研究移動相組成對游離常數的影響，我們測量不同比例（50-65%, v/v）甲醇—水混和物的pKa值。結果顯示RP-HPLC適合用於verapamil與trandolapril的高流量分析。這項方法可以應用於藥物製劑的分析且節省時間與花費。已經驗證可用來同時分析這些化合物的錠劑不受其他成分的干擾。"

The analysis of weakly basic drugs such as verapamil by reverse-phase liquid chromatography remains a problem, particularly when present in combination with other drugs such as amphoteric compounds like trandolapril. In this study, the simple, accurate, precise and fully validated RP-LC method for the simultaneous determination of verapamil and trandolapril in combined dosage forms has been developed. The LC method allowed quantitation over the ranges of 0.50-18.00 µg/mL and 0.05-1.00 µg/mL for verapamil and trandolapril, respectively. The detection limits were found to be 0.008 μg/mL and 0.018 μg/mL for verapamil and trandolapril, respectively. Moreover, pKa values of verapamil and trandolapril were determined via the dependence of the retention factor on the pH of the mobile phase for ionizable substances. The effect of the mobile phase composition on the ionization constant was studied by measuring the pKa at different methanol-water mixtures, ranging 50-65% (v/v). It was shown that RP-HPLC was suitable for the high throughput analysis of the combi-nation of verapamil and trandolapril. The method also allows a number of cost and time saving benefits and can be readily employed for the analysis of pharmaceutical formulations. The method has been verified, without any interference from excipients, for the concurrent analysis of these compounds in tablets.