以HPLC-UV方法對菲索非那定（Fexofenadine）及其合成中間產物進行分析之研究

Characterization and Determination of Fexofenadine with Its Synthetic Intermediate Compounds by HPLC-UV Method

菲索非那定(Fexofenadine)屬於第二代抗組胺藥物，是特非那定(terfenadine)在人體內的代謝產物，卻仍具有藥理活性。菲索非那定對季節性變態反應性鼻炎(AR)、特發性蕁麻疹療效突出；並且相對於特非那定，菲索非那定不會導致心臟QT間期延長、尖端扭轉型室速等室性心律失常副作用，即使口服劑量為推薦量的幾倍或同時服用影響代謝的藥物，也不會引起心臟的毒副作用。菲索非那定無法通過血腦屏障，無抗組胺藥的嗜睡副作用，在美國為飛行員抗過敏推薦用藥。本篇研究對鹽酸菲索非那定及其合成過程中的中間產物，建立以HPLC-UV方法進行特性分析。在最佳化情況下，可在15分鐘內對鹽酸菲索非那定與三種主要中間產物混合液分離而得到良好的層析圖譜，訊號與濃度線性關係測定的結果，為Y=1.103x10^3X-1.186x10^3，r=0.9999 (n=3)，具有良好的線性關係，而同日間精密度(Intra-day precision)與異日間精密度(Inter-day precision)之測定RSD分別為＋/-0.43%與＋/-0.28%，其準確度則與使用傳統非水滴定法測定結果具有一致性。使用本研究所建立的HPLC-UV分析方法，應用於對某藥廠製備的鹽酸菲索非那定受氧化劑、強酸、強鹼、熱降解、光降解等試驗結果之探討，發現該藥廠所製備之鹽酸菲索非那定具有良好的穩定性。

A simple and rapid isocratic HPLC-UV method for the routine quality control of fexofenadine hydrochloride in synthesis products has been established. By using triethylamine-phosphoric acid aqueous solution (0.10 mol/L) /methanol (45:55) mobile phase (flow rate 1.0 mL/min) and ODS column at ambient temperature, fexofenadine hydrochloride can be well separated from its 3 major synthetic intermediate impurities in 15 minutes. The representative linear equation of the method was Y=1.103x10^3x-1.186x10^3, where X is the concentration of fexofenadine hydrochloride and Y is the peak area, with correlation coefficient (R) of 0.9999 (n=3). The limit of quantitation (LOQ) and limit of detection (LOD) of the proposed method were 180 ng and 60 ng, respectively. The RSD of intra- and inter-day precision test of the method were 0.43% and 0.28%, respectively, which had shown great promise in the quality control routine analysis of fexofenadine hydrochloride. The proposed method was demonstrated in degradation test of fexofenadine hydrochloride.