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KMID : 0370220150590030091
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Yakhak Hoeji
2015 Volume.59 No. 3 p.91 ~ p.99
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Development of an Alternative Analytical Method without Related Substance Reference Standards for Fenofibrate in Korean Pharmacopoeia
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Kim Jung-Hyun
Kim Min-Young
Kwon Eun-Kyung
Lee Kwang-Moon
Choi Don-Woong
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Abstract
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Analytical method for related substances can be categorized into two methods depending on the necessity of reference standard (RS). The analytical method of related substances with RS is fast and accurate, but it’s very expensive and technically difficult to synthesize RS due to their complicated structure. Another method is using relative retention time (RRT) and relative response factor (RRF) which are already validated with RS. Validation of this method is not easy and time consuming, but once it has been developed, it can save cost and time. In this study, we developed the analytical method for related substances of fenofibrate using RRT and RRF. We validated the method by evaluating specificity, linearity, accuracy and precision according to the 「Manual for Guideline Application for Validation of Analytical Procedures」 of MFDS. Also, we calculated RRT and RRF between fenofibrate and fenofibrate related substances. The results of this study showed high specificity for fenofibrate and fenofibrate related substances. Correlation coefficient(r) of all substances were more than 0.99, and the recovery of fenofibrate, fenofibrate related substance I, II and III were 99.44%, 100.84%, 99.14% and 101.58%, respectively. Precision of fenofibrate and its related substances were ranged between RSD 0.29% and 0.93%. Quantification limits of fenofibrate, fenofibrate related substance I, II and III were determined to be 0.03 μg/ml, 0.05 μg/ml, 0.04 μg/ml and 0.02 μg/ml, respectively by confirming signal to noise ratio of each chromatogram. The RRT for fenofibrate related substance I, II and III were determined to be 0.35, 0.41 and 1.34, respectively. Also, the RRF for fenofibrate related substance I, II and III were determined to be 1.28, 0.98 and 0.79, respectively. The developed method was applied to determine contents for fenofibrate related substances in commercial fenofibrate (active pharmaceutical ingredient). As a result, developed analytical methods of related substances will be used for revising the monograph of fenofibrate in Korean Pharmacopoeia revision and contribute quality control of drugs by improving cost and time consuming problem of RS.
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KEYWORD
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Korean Pharmacopoeia, fenofibrate, related substances, impurity test, reference standard
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