Reliable and fast quantitative analysis of active ingredient in pharmaceutical suspension using Raman spectroscopy

The concentration of acetaminophen in a turbid pharmaceutical suspension has been measured successfully using Raman spectroscopy. The spectrometer was equipped with a large spot probe which enabled the coverage of a representative area during sampling. This wide area illumination (WAI) scheme (coverage area 28.3 mm2) for Raman data collection proved to be more reliable for the compositional determination of these pharmaceutical suspensions, especially when the samples were turbid. The reproducibility of measurement using the WAI scheme was compared to that of using a conventional small-spot scheme which employed a much smaller illumination area (about 100 microm spot size). A layer of isobutyric anhydride was placed in front of the sample vials to correct the variation in the Raman intensity due to the fluctuation of laser power. Corrections were accomplished using the isolated carbonyl band of isobutyric anhydride. The acetaminophen concentrations of prediction samples were accurately estimated using a partial least squares (PLS) calibration model. The prediction accuracy was maintained even with changes in laser power. It was noted that the prediction performance was somewhat degraded for turbid suspensions with high acetaminophen contents. When comparing the results of reproducibility obtained with the WAI scheme and those obtained using the conventional scheme, it was concluded that the quantitative determination of the active pharmaceutical ingredient (API) in turbid suspensions is much improved when employing a larger laser coverage area. This is presumably due to the improvement in representative sampling.