Development, cross-validation and greenness assessment of capillary electrophoresis method for determination of ALP in pharmaceutical dosage forms – an alternative to liquid chromatography†

Breast cancer treatment has made tremendous progress in recent years and new therapies are emerging continuously. Alpelisib (ALP) is a novel phosphoinositide-3-kinase (PI3K) inhibitor recently approved for human receptor-positive, human epidermal growth factor receptor 2-negative, PIK3CA-mutated metastatic breast cancer in combination with fulvestrant. ALP has been the subject of only a limited number of preclinical in vitro and in vivo studies using different chromatographic techniques. However, no research has been published on analyzing ALP using capillary electrophoresis (CE). The absence of pharmacopoeial monographs for ALP in both the European and United States Pharmacopoeias highlights the urgent need to develop a reliable analytical method for its quality control in both industry and regulatory authorities. In this work, we have developed a first-ever CE method for the determination of ALP in pharmaceutical dosage forms in just 1.4 minutes. This was achieved with a 25 mM borate buffer at pH 9.3, 30 kV separation voltage and 30 °C capillary temperature. The proposed method was validated according to the ICH guidelines regarding selectivity, linearity (r = 0.9988), precision (RSD < 5.9%), accuracy (bias < 3.0%) and robustness (RSD < 3.2%). It was applied to the pharmaceutical dosage form of ALP and was shown to be suitable for the reliable determination of ALP. Furthermore, to demonstrate the applicability of the CE as an alternative technique to more commonly used HPLC in the analysis of drugs, cross-validation of CE and HPLC methods was performed. Bland–Altman analysis showed that the average difference in determined concentrations between CE and HPLC over a range of 10–100 μg mL⁻¹ was 0.87 μg mL⁻¹ (p = 0.6390, N = 19) meaning that there is no difference in the performance of CE and HPLC in the determination of ALP in pharmaceutical dosage forms. The environmental impact of both methods was assessed using AGREE software and scores for CE and HPLC were calculated to be 0.74 and 0.51, respectively. Because of equally reliable analytical performance and greener analysis, CE should be considered as an alternative technique to HPLC in the analysis of ALP pharmaceutical dosage forms.