利用HPLC 及螢光分光光度計研究Phenazopyridine Hydrochloride 之強酸／熱降解及分解產物／不純物概況   全文下載

Study of Forced-Acid/Heat Degradation and Degradant/Impurity Profile of Phenazopyridine Hydrochloride through HPLC and Spectrofluorimetric Analyses

此篇論文包括兩個相關主題。首先，有關phenazopyridine hydrochloride（PAP）的強酸/ 熱降解研究，該反應途徑係經不同標準被證明。開發以三波長為基礎的反相HPLC 法，配合等梯度移動相系統（乙?/pH 4 醋酸緩衝溶液，1/1，v/v），並以此安定性指標HPLC 法應用在PAP 及其相關分解產物/ 不純物之多重分析。在流速1 mL/min 下，分析時間少於8 min。分解產物/ 不純物之最低檢測極限及最低定量極限分別在0.02-0.1 及0.06-0.3 μg/mL。原料藥及錠狀中PAP 不純物概況可被評估，且最低可檢測出0.03%至0.005% 的程度。第二個主題探討螢光分光光度計法定量微量濃度之酚（PH）及2,6-diaminopyridine（DAP），此二物質係為PAP 的分解產物/ 不純物。此法乃依據酸性乙醇溶液（DAP）或酸性水溶液（PH）中天然螢光之計算，可應用於檢查原料藥及錠狀型式PAP 之不純物/ 穩定性。"

The article handles two related subjects. First, it’s the study of forced-acid/heat degradation of phenazopyridine HCl (PAP). The reaction pathway was evidenced with different criteria. A three wavelengths-based reversed phase HPLC method with an isocratic mobile phase system (acetonitrile:acetate buffer of pH 4, 1:1, v/v) was developed as a stability-indicating assay of particular application for simultaneous determination of PAP and its related degradation products/impurity. The analysis time was less than 8 min at a flow rate of 1 mL min-1. The detection and quantification limits of degradation products/impurity were in the ranges of 0.02-0.1 and 0.06-0.3 μg mL-1, respectively. The impurity profile of PAP in drug substance and tablets was investigated and could be determined down to a level between 0.03% and 0.005%. The second subject deals with establishment of spectrofluorimetric method for quantification of phenol (PH) and 2,6-diaminopyridine (DAP), as degradant/impurity in PAP, at trace concentrations. The method is based on measurement of the native fluorescence in acidic ethanol solution (DAP) or in aqueous acidic solution (PH). The method was applied to check the purity/stability of PAP in drug substance and in tablets dosage form.