Development and validation of a UPLC-MS method for determination of atazanavir sulfate by the “analytical quality by design” approach

Abstract

A UPLC-MS method for the estimation of atazanavir sulfate was developed using the "analytical quality by design" approach. The critical chromatographic quality attributes identified were retention time, theoretical plates and peak tailing. The critical method parameters established were percent of organic modifier, flow rate and injection volume. Optimization performed using Box-Behnken Design (BBD) established 10 % organic modifier, 0.4 mL min -1 flow rate and 6-µL injection volume as the optimum method conditions. Atazanavir sulfate eluted at 5.19 min without any interference. Method validation followed international guidelines. The method has proven linearity in the range of 10-90 µg mL -1 . Recovery was between 100.2-101.0 % and precision within the accepted limits (RSD 0.2-0.7 %). LOD and LOQ were 2.68 and 8.14 µg mL -1 , resp. Stress testing stability studies showed atazanavir sulfate to degrade under acidic and basic conditions. The suggested technique is simple, rapid and sustainable. It is, therefore, suggested for routine analysis of atazanavir sulfate.

Quality-by-design in pharmaceutical development: From current perspectives to practical applications

“…In the case of an HPLC/UHPLC method, these CMAs can be peak symmetry, tailing factor, peak width, analysis time, the resolution between two peaks, theoretical plates, signal-to-noise ratio, etc. (40)(41)(42)(43). In the case of a complex matrix (e.g., plant extract, biological matrix) the definition of CMA can be difficult (if in any condition the CMA varies between the preferred intervals, it cannot be considered a CMA) (44).…”

“…In a recent study published by Saha et al (42) a simple, rapid and robust UPLC-MS method was developed for atazanavir sulphate using the AQbD approach. Implementing a combined technique of Ishikawa followed by FMEA risk analysis, factors (percent of organic modifier, flow rate and injection volume) that critically affect selected responses (analyte retention time, theoretical plate number, peak tailing and column) have been identified.…”

“…MODR is the region of robustness, where the effect of CMPs (input variables) on CMAs meets the desired analytical parameters drafted by ATPs (59). Determination of MODR during the method development phase can substitute the robustness testing at the end of the method validation (42). The importance of the design space is highlighted when transferring methods between laboratories; additional validation steps are required only if the condition is moved out of the design space.…”

“…In order to better visualize the effects of the input variables (such as pH, temperature, flow rate, etc.) on CMAs, response surface analysis (2D or 3D response surface plot) can be applied, which shows the complex, non-linear interactions between the studied factors on quality performances (42,61). A general workflow presenting the steps of AQbD is illustrated in Scheme 2 (28,62,63).…”

Implementation of analytical quality‐by‐design and green analytical chemistry approaches for the development of robust and ecofriendly UHPLC analytical method for quantification of chrysin

“…Accordingly, this calls for development of a robust and sensitive LC-based analytical method for CHN [7]. The need for ultrafast separation, coupled with high efficiency and resolution, has leads to the emergence of an environment-friendly, cost-effective, and fast analytical technique of UHPLC [9][10][11]. Its distinct edge over traditional HPLC procedures is attributed to submicron sized particles of the stationary phase (i.e., <2 µm), leading eventually to the reduced sample run time, reduced consumption of solvents, lower back pressure, increased method efficiency, and reduction in the total expenditure involved during the analytical process [12][13][14][15].…”