QbD‐oriented development and validation of a bioanalytical method for nevirapine with enhanced liquid–liquid extraction and chromatographic separation

Abstract

The present studies describe the systematic quality by design (QbD)-oriented development and validation of a simple, rapid, sensitive and cost-effective reversed-phase HPLC bioanalytical method for nevirapine in rat plasma. Chromatographic separation was carried out on a C18 column using isocratic 68:9:23% v/v elution of methanol, acetonitrile and water (pH 3, adjusted by orthophosphoric acid) at a flow rate of 1.0 mL/min using UV detection at 230 nm. A Box-Behnken design was applied for chromatographic method optimization taking mobile phase ratio, pH and flow rate as the critical method parameters (CMPs) from screening studies. Peak area, retention time, theoretical plates and peak tailing were measured as the critical analytical attributes (CAAs). Further, the bioanalytical liquid-liquid extraction process was optimized using an optimal design by selecting extraction time, centrifugation speed and temperature as the CMPs for percentage recovery of nevirapine as the CAA. The search for an optimum chromatographic solution was conducted through numerical desirability function. Validation studies performed as per the US Food and Drug Administration requirements revealed results within the acceptance limit. In a nutshell, the studies successfully demonstrate the utility of analytical QbD approach for the rational development of a bioanalytical method with enhanced chromatographic separation and recovery of nevirapine in rat plasma. Copyright © 2015 John Wiley & Sons, Ltd.

Development of a validated liquid chromatographic method for quantification of sorafenib tosylate in the presence of stress‐induced degradation products and in biological matrix employing analytical quality by design approach

“…For systematic development of the analytical and bioanalytical methods of SFN, the analytical target profile (ATP) was defined, delineating all of the desired quality characteristics of the analytical method employing the principles of the AQbD approach (Beg, Chaudhary, et al, ; Beg, Sharma, Katare, Lohan, & Singh, ; Khurana et al, , Sandhu, Beg, Katare, & Singh, ). Various elements of ATP were enlisted (Table S1 in the Supporting Information).…”

“…Factor screening of various CMPs, potentially influencing the chosen CAAs, was performed employing Taguchi design for seven factors at two levels (Beg, Chaudhary, et al, ; Beg, Sharma, et al, ). Table depicts the design matrix adopted during the screening studies, enlisting the studied factors and decoding their respective low and high levels.…”

“…minimization of peak tailing and R t , and maximization of peak area and number of theoretical plates. Further, graphical optimization was also conducted to demarcate the optimal method operable design region, facilitating the location of the optimized solution (Beg, Chaudhary, et al, ; Beg, Sharma, et al, ).…”

Determination of a metabolite of nifursol in foodstuffs of animal origin by liquid–liquid extraction and liquid chromatography with tandem mass spectrometry

“…Sample purification methods included LLE , and SPE . Considering that SPE is more expensive than LLE, we used LLE for sample purification.…”

Development and validation of a quality by design enabled robust LC method for estimation of daptomycin in pharmaceutical dosage form

“…The ICH Q8 (R2) provides flexibility to pharmaceutical research and development community by allowing exploring the basic and vital steps of the QbD approach . This rapid QbD approach is not only time‐efficient and economic during the analytical development phase but also produces commensurate results those obtained by traditional extensive QbD workflow . It has only three but vital steps such as the establishment of analytical target profile (ATP) and critical analytical attributes (CAAs) considering the critical method variables (CMVs), selection of a befitting analytical technique and defining analytical control strategies (ACS).…”