Method development and validation of an analytical quality by design ultrafast liquid chromatographic method for the determination of bedaquiline from pharmaceutical bulk and nanoemulsions

Abstract

Bedaquiline (BDQ) is a drug used to treat multidrug‐resistant tuberculosis (MDR‐TB). It exhibits exposure‐dependent efficacy in eliminating Mycobacterium tuberculosis (Mtb). An easy, efficient and precise reverse‐phase ultrafast liquid chromatography (RP‐UFLC) method was developed to validate the free base of the antitubercular medication BDQ. BDQ was separated using a 10:90 v/v mobile phase of ammonium acetate buffer solution (pH = 5.4) and high‐performance liquid chromatography–grade methanol, with a flow rate of 1.5 mL/min and a UV detection wavelength of 226 nm. By using the Box–Behnken design (BBD) and response surface methodology (RSM), the method was optimised by varying critical analytical attributes (CAA) and critical performance attributes (CPAs) namely ammonium acetate fraction (%), flow rate (ml/min), buffer system molarity (M) and pH. BDQ was eluted at 7.5 min utilising isocratic elution. The method was linear in the concentration range of 0.5–300 μg/mL with limit of detection values of 0.039 μg/mL and limit of quantification of 0.12 μg/mL. The results indicate that this validated method can be used as an alternative method for assay of BDQ.