Augmentation of Brexpiprazole fluorescence through photoinduced electron transfer inhibition for the sensitive spectrofluorimetric assay of pharmaceutical dosage forms and spiked human plasma: Application to content uniformity testing

Brexpiprazole (BRX) is a new antipsychotic drug that recently was used in the treatment of schizophrenia and other psychosis. The presence of benzothiophene ring in its chemical structure makes BRX naturally fluoresces. However, the native fluorescence of the drug was low in neutral or alkaline medium owing to the occurrence of photoinduced electron transfer (PET) from the nitrogen of the piperazine ring to the benzothiophene ring. Protonation of this nitrogen atom using sulfuric acid could efficiently block PET process and thus retaining the strong fluorescence of the compound. Accordingly, a straightforward, highly sensitive, fast and green spectrofluorimetric approach was established for BRX determination. In 1.0 M sulfuric acid solution, BRX exhibited significant native fluorescence measured at emission wavelength of 390 nm after excitation at 333 nm. ICH requirements were used to evaluate the method. The fluorescence intensity and BRX concentration were found to be correlated linearly within the range of 5-220 ng mL-1 with a coefficient of correlation 0.9999. The limit of quantitation was 2.38 ng mL-1 while limit of detection was 0.78 ng mL-1. The developed approach was successfully used to analyze BRX in biological fluids and pharmaceutical dosage form. The suggested approach worked well when applied for testing the uniformity of content.