替吉奥仿制药与原研药的体外一致性评价

In Vitro Consistency Evaluation Between Generic and Original TS-1 Preparations

关键词:  替吉奥  一致性评价  溶出度  溶出曲线

Key words:  TS-1  consistency evaluation  dissolution  dissolution curve

摘要:

目的 建立替吉奥制剂体外溶出曲线的测定方法，评价国内10种替吉奥仿制药与原研药体外溶出曲线的相似性。方法 采用高效液相色谱法建立替加氟（tegafluorogen，FT）、吉美嘧啶（gemiracil，CDHP）和奥替拉西钾（oteracil potassium，OXO）的定量测定方法。色谱柱为Agilent ZORBAX SB-C₁₈，流动相为磷酸盐缓冲液-乙腈（90：10），等度洗脱，流速1 mL·min^-1，检测波长在0~5 min为240 nm，5~9 min为288 nm，9~14 min为270 nm，进样量10 μL。采用转篮法测定各制剂在pH 1.2盐酸溶液、pH 4.5醋酸盐缓冲液、pH 6.8磷酸盐缓冲液和水4种不同溶出介质中的标准溶出曲线，并通过相似因子（f₂）评价仿制药与原研药溶出曲线的相似性。结果 其中8种替吉奥仿制药与原研药的体外溶出行为相似。结论 该方法适用于替吉奥制剂的溶出曲线测定，可为替吉奥制剂质量一致性评价提供参考。

Abstract:

OBJECTIVE To establish a method for the determination of in vitro dissolution curve of TS-1 preparations and to evaluate the consistency of in vitro dissolution curve between 10 domestic TS-1 generics and the original preparation. METHODS Quantitative method for the determination of tegafluorogen(FT), gemiracil(CDHP) and oteracil potassium(OXO) was established by HPLC. The column was Agilent ZORBAX SB-C₁₈. The mobile phase was consist of phosphate buffer and acetonitrile(90:10) with a flow rate of 1 mL·min^-1 under isaratic elution. The detection wavelength was 240 nm at 0-5 min, 288 nm at 5-9 min, and 270 nm at 9-14 min. Sample injection volume was 10 μL. The standard dissolution curves of each preparation in four different dissolution media, namely pH 1.2 hydrochloric acid solution, pH 4.5 acetate buffer, pH 6.8 phosphate buffer and water, were determined by the basket method. The similarity between the dissolution curves of the generic drug and the original drug were evaluated by the similarity factor(f₂). RESULTS The dissolution behavior of 8 domestic TS-1 generics was consistent with that of the original preparation. CONCLUSION The established method can efficiently determine the dissolution curve and provide reference for the quality consistency evaluation of TS-1 preparations.