Quantitative analysis of active compounds in pharmaceutical preparations by use of attenuated total-reflection Fourier transform mid-infrared spectrophotometry and the internal standard method

Abstract

A new method is presented for the quantitative analysis of compounds in pharmaceutical preparations – Fourier transform (FT) mid-infrared (MIR) spectroscopy with an attenuated total reflection (ATR) module. Reduction of the quantity of overlapping absorption bands, by interaction of the compound of interest with an appropriate solvent, and the employment of an internal standard (IS), makes MIR suitable for quantitative analysis.

Vigabatrin, as active compound in vigabatrin 100-mg capsules, was used as a model compound for the development of the method. Vigabatrin was extracted from the capsule content with water after addition of a sodium thiosulfate IS solution. The extract was concentrated by volume reduction and applied to the FTMIR–ATR module. Concentrations of unknown samples were calculated from the ratio of the vigabatrin band area (1321–1610 cm^–1) and the IS band area (883–1215 cm^–1) using a calibration standard. The ratio of the area of the vigabatrin peak to that of the IS was linear with the concentration in the range of interest (90–110 mg, in twofold; n=2). The accuracy of the method in this range was 99.7–100.5% (n=5) with a variability of 0.4–1.3% (n=5).

The comparison of the presented method with an HPLC assay showed similar results; the analysis of five vigabatrin 100-mg capsules resulted in a mean concentration of 102 mg with a variation of 2% with both methods.