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.
GF120918; Solid dispersion; Dissolution; Hydroxylation; HPLC–UV
Citation: Emilia Sawicki, Michel J. Hillebrand, Hilde Rosing, Jan H.M. Schellens, Bastiaan Nuijen, Jos H. Beijnen
Validation Of A Liquid Chromatographic Method For The Pharmaceutical Quality Control Of Products Containing Elacridar http://dx.doi.org/10.1016/j.jpha.2016.04.005
Received: 3 February 2016, Revised: 12 April 2016, Accepted: 13 April 2016, Available online: 23 April 2016
Copyright: © 2016 Xi'an Jiaotong University. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
An HPLC–UV method was developed and validated for the pharmaceutical quality control of a drug powder, an amorphous solid dispersion and a tablet formulation with elacridar as the API. The HPLC–UV method can be used to analyze the content, purity and dissolution. Light induces elacridar hydroxylation in aqueous samples and therefore light protection is required.