Determination of active ingredient within pharmaceutical preparations using flow injection mass spectrometry

Two separate pharmaceutical blends, one containing 2% caffeine by weight, the other containing 2% creatine by weight, and 200 mg caffeine tablets were examined in this study. The purpose of the analyses was to determine the feasibility of using flow injection mass spectrometry for the quantitative analysis of active ingredient within a drug product or other form of pharmaceutical preparation. For more precise and accurate measurements, it was necessary to incorporate an internal reference within the samples. Further, flow injection analysis showed to provide quicker, more facile method development than the application of chromatographic separation. Samples were analyzed over an analyte concentration range of 5.0-15.0 μg/mL. Analyte selectivity was obtained through the observance of the (M + H)+ ions generated by positive electrospray ionization of each of the analytes (m/z 195 for caffeine and m/z 132 for creatine), and accurate quantitation was achieved by determining the ratio of the analyte response versus the response of the incorporated reference compound. Sample-to-sample precision in these measurements was less than 3%, recovery values were shown to be accurate to within ±3% of the actual values, and both analytical methods proved to be linear over the assay range (R2 ≥ 0.999). Due to the excellent selectivity and low detection limits available to mass spectrometric detection, flow injection mass spectrometric analysis could be particularly applicable for analysis of formulations that contain either low doses of active ingredient, active ingredient with low solubility, or active ingredient that does not possess a strong chromophore. Additionally, this type of methodology shows to be conducive for rapid method development.