Development and optimization of a multivariate RP-UPLC method for determination of telmisartan and its related substances by applying a two-level factorial design approach: application to quality control study

Abstract

Herein we report a simple, specific and rapid reverse-phase ultraperformance liquid chromatographic (RP-UPLC) method that was developed and optimized by using a two-level factorial design approach for telmisartan (TLM) and its eight critical process-related impurities. This method has excellent resolution of critical impurities, low cost of analysis and a reduced run time; moreover, it shows excellent resolution by using a BEH C18 column (100 × 2.1 mm, 1.7 μm) with phosphate buffer (10 mM) as mobile phase A (pH = 2.5); acetonitrile : methanol : water as mobile phase B (75 : 15 : 10 v/v/v); column oven temperature, 30 °C; flow rate, 0.33 mL min⁻¹; and 2.0 μL injection volume, which is monitored at 235 nm. Furthermore, the peak purity was checked for specificity, and the robustness of the method was enhanced by applying a two-level factorial design. In this design, the influence of different factors such as % methanol in mobile phase B, flow, column oven temperature, pH of the mobile phase on the responses such as resolution between impurity E and TLM, and % recovery of impurity E was investigated. Based on the response of the design, the developed method is precise, accurate, linear, successfully implemented for monitoring the reactions in R&D laboratories, and thus suitable for quality control purposes as well as the stability analysis of TLM-active pharmaceutical ingredients.