應用溴甲酚紫及分光光度法開發並確效靈敏度高且具選擇性之樂命達製劑檢驗方法   全文下載

Development and Validation of Spectrophotometric Methods for the Sensitive and Selective Determination of Lamotrigine in Pharmaceuticals Using Bromocresol Purple

開發並確效三種簡易、具選擇性且敏感度高的樂命達（lamotrigine, LmT）純品及錠劑檢驗方法。第一種方法（方法A）係將樂命達和染劑溴甲酚紫（BCP）於pH值2.40 ± 0.01 合成離子對複合物，並以二氯甲烷（dichloromethane, DCm）萃取，在波長410 nm時測定該黃色離子對複合物之吸光值。第二與第三種測定法（方法B和C），則是分別以乙醇、醇化氫氧化鉀解離藥品和染劑合成的離子對複合物，在波長 410 nm 、600 nm 時測定其吸光值。最適化條件下， 方法A 、B 、C分別於2.0-20.0 μg/mL 、150-1500 ng/mL以及50-600 ng/mL的濃度範圍內符合比爾吸收定律（Beer’s law）；相對應之莫耳吸光值（molar absorptivity values）分別為 1.018 × 104、1.43 × 105以及 4.21 × 105 L/mol/cm；三種方法之桑德爾靈敏度值（Sandell sensitivity value）依序為0.0252 、0.0018 和0.0006 μg/cm2；三種方法之偵測及定量極限均陳述於報告中。依賈伯法（Job’s method） 推論，方法A中合成的離子對複合物莫耳比為1:1，其計算用穩定常數亦陳述於報告中。線性範圍內，以同日內與異日間分析評估各方法之準確度和精密度；三種方法之平均準確值（mean accuracy values）分別為99.50 ± 1.09% 、99.99 ± 1.11% 以及 100.72 ± 0.62%；相對誤差? 2.57%，相對標準差? 2.01%。三種方法於原料藥粉和錠劑之應用亦有敘述。"

Three simple, selective and sensitive methods have been developed and validated for the determination of lamotrigine (LMT) in pure drug and in tablets. The first method (method A) is based on the formation of ion-pair complex between LMT and the dye, bromocresol purple (BCP) at pH 2.40 ± 0.01 which was extracted into dichloromethane (DCM) and the absorbance of yellow ion-pair complex was measured at 410 nm. In the second and third methods (method B and method C), the drug-dye ion-pair was dissolved either in ethanol and the resulting acid form of the dye was measured at 410 nm or in ethanolic potassium hydroxide and the resulting base form of the dye was measured at 600 nm. Under the optimized conditions, Beer’s law was obeyed over 2.0-20.0 μg/mL, 150-1500 ng/mL and 50-600 ng/mL for method A, method B and method C, respectively, and the corresponding molar absorptivity values were 1.018 × 104, 1.43 × 105 and 4.21 × 105 L/mol/cm. The Sandell sensitivity values of 0.0252, 0.0018 and 0.0006 μg/cm2 for method A, method B and method C, respectively, and the corresponding values for limits of detection and quantification were also reported for all three methods. The molar ratio of the formed ion-pair complex was found to be 1: 1 as deduced by Job’s method for method A, and the calculated stability constant was also reported. Over the linear ranges applicable, the accuracy and precision of the methods were evaluated on intra-day and inter-day basis; the reported mean accuracy values are 99.50 ± 1.09%, 99.99 ± 1.11% and 100.72 ± 0.62% for method A, method B, and method C, respectively; the relative error (RE) was ≤ 2.57% and the relative standard deviation (RSD) was ≤ 2.01%. Application of the proposed methods to bulk powder and commercial pharmaceutical tablets are also presented.