Ultraviolet spectrophotometry for the determination of benperidol by a difference procedure and for the elucidation of its polymorphic structures

Abstract

Benperidol contains two chromophores separated by a non-conjugated system. Its ultraviolet absorption spectrum, in acidic or neutral aqueous solution, shows maxima due to the p-fluoroacetophenone chromophore (at 249 nm) and to the benzimidazolone chromophore (at 232 and 279 nm). In alkali, owing to ionisation, there is a bathochromic shift of the benzimidazolone absorption, and peaks occur at 220, 248 and 288 nm. An apparent hyperchromic effect at 248 nm is caused by the overlapping of peaks from the two chromophores. A procedure is proposed for determining benperidol in tablets by measuring the difference in absorbance at 292 nm of solutions prepared in alkali and in acid. This can eliminate background interference, and hence avoid preliminary purification steps.

Infrared spectra indicate that benperidol can act as a zwitterion. Ultraviolet absorption spectra of benperidol in organic solvents show marked bathochromic shifts of the longer wavelength benzimidazolone maximum, compared with spectra in acidic or neutral aqueous solution. In ethers, the shift is of the same magnitude as that produced in aqueous alkali and probably indicates hydrogen bonding with the enol form. Alcohols can stabilise the zwitterion by hydrogen bonding with the oxygen of the —NC—O^– grouping, which would explain the formation of a polymorph with no amide absorption on recrystallisation from isopropanol.