Validation of a liquid chromatographic method for the pharmaceutical quality control of products containing elacridar  

作　　者：Emilia Sawicki Michel J.Hillebrand Hilde Rosing Jan H.M.Schellens Bastiaan Nuijen Jos H.Beijnen 

机构地区：[1]Department of Pharmacy & Pharmacology,The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital [2]Division of Clinical Pharmacology,Department of Medical Oncology,The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital [3]Division of Pharmacoepidemiology & Clinical Pharmacology.Department of Pharmaceutical Sciences,Faculty of Science.Utrecht University

出　　处：《Journal of Pharmaceutical Analysis》2016年第4期268-275,共8页药物分析学报（英文版）

摘　　要：Many anticancer drugs have an impaired bioavailability and poor brain penetration because they are substrates to drug efflux pumps such as P-glycoprotein and Breast Cancer Resistance Protein.Elacridar is a strong inhibitor of these two drug efflux pumps and therefore has great potential to improve oral absorption and brain penetration of many anticancer drugs.Currently,a clinical formulation of elacridar is unavailable and therefore the pharmaceutical development of a drug product is highly warranted.This also necessitates the availability of an analytical method for its quality control.A reverse-phase high-performance liquid chromatographic method with ultraviolet detection was developed for the pharmaceutical quality control of products containing elacridar as the active pharmaceutical ingredient.The analytical method was validated for linearity,accuracy,precision,selectivity,carry-over,stability of stock and reference solutions,stability of the final extract,stability-indicating capability and impurity testing.We found that elacridar is unstable in aqueous solutions that are exposed to light because a hydroxylation product of elacridar is formed.Therefore,sample solutions with elacridar must be protected from light.Many anticancer drugs have an impaired bioavailability and poor brain penetration because they are substrates to drug efflux pumps such as P-glycoprotein and Breast Cancer Resistance Protein.Elacridar is a strong inhibitor of these two drug efflux pumps and therefore has great potential to improve oral absorption and brain penetration of many anticancer drugs.Currently,a clinical formulation of elacridar is unavailable and therefore the pharmaceutical development of a drug product is highly warranted.This also necessitates the availability of an analytical method for its quality control.A reverse-phase high-performance liquid chromatographic method with ultraviolet detection was developed for the pharmaceutical quality control of products containing elacridar as the active pharmaceutical ingredient.The analytical method was validated for linearity,accuracy,precision,selectivity,carry-over,stability of stock and reference solutions,stability of the final extract,stability-indicating capability and impurity testing.We found that elacridar is unstable in aqueous solutions that are exposed to light because a hydroxylation product of elacridar is formed.Therefore,sample solutions with elacridar must be protected from light.

关 键 词：GF120918 Solid dispersion Dissolution Hydroxylation HPLC-UV 

分 类 号：R927[医药卫生—药学] O657.72[理学—分析化学]