Development and validation of RP-HPLC method for estimation of brexpiprazole in its bulk and tablet dosage form using Quality by Design approach

Amol S Jagdale,Poonam M Bachhav,Rupali V Nirmal,Nilesh S Pendbhaje,Dayandeo B Sumbre

doi:10.1186/s43094-021-00293-5

Abstract

BackgroundA new, sensitive, suitable, clear, accurate, and robust reversed-phase high-performance liquid chromatography (RP-HPLC) method for the determination of brexpiprazole in bulk drug and tablet formulation was developed and validated in this research. Surface methodology was used to optimize the data, with a three-level Box-Behnken design. Methanol concentration in the mobile phase, flow rate, and pH were chosen as the three variables. The separation was performed using an HPLC method with a UV detector and Openlab EZchrom program, as well as a Water spherisorb C18 column (100 mm × 4.6; 5m). Acetonitrile was pumped at a flow rate of 1.0 mL/min with a 10 mM phosphate buffer balanced to a pH of 2.50.05 by diluted OPA (65:35% v/v) and detected at 216 nm.ResultThe developed RP-HPLC method yielded a suitable retention time for brexpiprazole of 4.22 min, which was optimized using the Design Expert-12 software. The linearity of the established method was verified with a correlation coefficient (r2) of 0.999 over the concentration range of 5.05–75.75 g/mL. For API and formulation, the percent assay was 99.46% and 100.91%, respectively. The percentage RSD for the method’s precision was found to be less than 2.0%. The percentage recoveries were discovered to be between 99.38 and 101.07%. 0.64 μg/mL and 1.95 μg/mL were found to be the LOD and LOQ, respectively.ConclusionThe developed and validated RP-HPLC system takes less time and can be used in the industry for routine quality control/analysis of bulk drug and marketed brexpiprazole products.Graphical abstract

Highlights

A new, sensitive, suitable, clear, accurate, and robust reversed-phase high-performance liquid chromatography (RP-HPLC) method for the determination of brexpiprazole in bulk drug and tablet formulation was developed and validated in this research
Brexpiprazole is 7-[4-[4-(1-benzothiophen-4-yl) piperazin-1-yl] piperazin-1-yl] piperazin-1-yl] piperazin1-yl] piperazin-1-yl] piperazin-1-yl] piperazin-1 butoxy] The United States Food and Drug Administration (USFDA) approved quinolin-2 (1H)-one in 2015, and it is marketed as Rexulti, a generic name coined by Otsuka in Japan and marketed by Lundbeck in the USA for the treatment of schizophrenia as a
Detection It may be calculated based on the standard deviation (SD) of the response and slope of the curve (S)

Summary

Introduction

A new, sensitive, suitable, clear, accurate, and robust reversed-phase high-performance liquid chromatography (RP-HPLC) method for the determination of brexpiprazole in bulk drug and tablet formulation was developed and validated in this research. Methanol concentration in the mobile phase, flow rate, and pH were chosen as the three variables. Acetonitrile was pumped at a flow rate of 1.0 mL/min with a 10 mM phosphate buffer balanced to a pH of 2.50.05 by diluted OPA (65:35% v/v) and detected at 216 nm. According to a literature review, there are few publications on UV-visible spectroscopy and HPLC, but no one has used Quality by Design. To ensure process consistency throughout the product lifecycle, simple validated RP-HPLC methods for the determination of brexpiprazole in pharmaceutical dosage forms must be established using the Quality by Design (QbD) approach as per ICH Q8 (R2) guidelines [8, 15–19]

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