Development and validation of a near-infrared method for the quantitation of caffeine in intact single tablets.

A near-infrared spectroscopic method was developed and validated for determining the caffeine concentration of single and intact tablets in a Finnish pharmaceutical product containing 58.82% (m/m) caffeine.The spectral region of interest contained a total of 474 data points. The second derivative of Savitsky-Golay, a standard normal variate, and mean centering were used as spectral preprocessing options. The feasibility study showed nonuniformity of caffeine repartition within each tablet. Thus, spectra were recorded from both faces of the tablets, and the analysis result for a single tablet was reported as the average of both face determinations. Precision of the method was validated because the relative standard deviations from repeatability and intermediate precision tests were below 0.75% (m/m). Accuracy validation proved that the NIR results were not significantly different (P = 0.09, n = 12) from the results obtained with the reference HPLC method. The limit of quantification for caffeine was 13.7% (m/m) in the tablets. The method was found to be unaffected by NIR source replacement, but the repeatability of the results was affected if the sample holder was not placed in the correct position in the light beam. Routine NIR analysis of caffeine in tablet form was found to be more flexible and much faster than that performed with the HPLC method.