QbD-Driven Development and Validation of a Bioanalytical LC–MS Method for Quantification of Fluoxetine in Human Plasma

Abstract

The current studies describe the Quality by Design (QbD)-based development and validation of a LC-MS-MS method for quantification of fluoxetine in human plasma using fluoxetine-D5 as an internal standard (IS). Solid-phase extraction was employed for sample preparation, and linearity was observed for drug concentrations ranging between 2 and 30 ng/mL. Systematic optimization of the method was carried out by employing Box-Behnken design with mobile phase flow rate (X1), pH (X2) and mobile phase composition (X3) as the method variables, followed by evaluating retention time (Rt) (Y1) and peak area (Y2) as the responses. The optimization studies revealed reduction in the variability associated with the method variables for improving the method robustness. Validation studies of the developed method revealed good linearity, accuracy, precision, selectivity and sensitivity of fluoxetine in human plasma. Stability studies performed in human plasma through freeze-thaw, bench-top, short-term and long-term cycles, and autosampler stability revealed lack of any change in the percent recovery of the drug. In a nutshell, the developed method demonstrated satisfactory results for analysis of fluoxetine in human plasma with plausible utility in pharmacokinetic and bioequivalence studies.

Recent advances in liquid chromatographic methods for the determination of selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors

“…In the HPLC method reported by Hasnain et al (), human plasma samples containing fluoxetine and the IS were subjected to SPE and evaporation–reconstitution processes for the whole preparation procedure, which significantly minimized matrix effects. The authors applied quality by design‐based principles and approaches into the discovery and optimization of the critical experimental parameters, thereby enhancing the understanding of the relationship and interactions between those parameters.…”

A systematized and chemometrics‐assisted liquid chromatography coupled with tandem mass spectrometry method for quantification of aripiprazole in implantable microparticles in rat plasma from pharmacokinetic study

“…BBD has an advantage over other designs that it requires less number of experiments, thus considerably saving time and effort [18, 19]. A score of research reports is the testimony of having demonstrated the utility of experimental designs in analytical method development [20–31]. For the present study survey of literature revealed that not a single bioanalytical method for ARIP assessed the robustness using the DoE approach which in turn may influence method performance over time.…”

Box-Behnken Assisted Validation and Optimization of an RP-HPLC Method for Simultaneous Determination of Domperidone and Lansoprazole

“…Additionally, these techniques offer minimal data on how the different parameters listed above interact with, and ultimately influence, each other. In the past, research has been conducted on the development and application of retaliation surface methodologies for the quantification of various compounds [23][24][25][26][27][28][29][30][31][32][33][34]. Therefore, this research was focused on the development of a Box-Behnken-optimized RP-HPLC method for the quantification of domperidone and lansoprazole in new and unusual solvent systems.…”