Optimization of Analytical Method for Simultaneous Determination of Acetaminophen, Caffeine, and Aspirin in Tablet Dosage Form

A combination of acetaminophen, caffeine, and aspirin in tablets is present in the United States Pharmacopoeia (USP42). A method of analysis for the simultaneous assay of the three analytes by high-performance liquid chromatography (HPLC) recommended in the monograph by using benzoic acid as an internal standard, which is chromatographically separated last in the chromatogram. In the current work, an optimization experiment was conducted to validate the analytical method without the internal standard, in order to shorten the chromatogram runtime. The mobile phase represented filtered degassed mixture of methanol, glacial acetic acid, and water (28:3:69 v/v). The HPLC device was operated at a flow rate of 2.0 mL/min and a column temperature of 45 degrees C. The injection volume was 10 mu L. Acetaminophen, aspirin, and caffeine were detected at 275 nm UV wavelength. A Symmetry C18 HPLC column with length 150 mm, internal diameter of 4.6 mm, and particle size of 5 mu m was used. The method is specific, with no interference between the analyte peaks, and it is linear in the range of 0.625 to1.870 mg/mL for acetaminophen, 0.625 to 1.870 mg/mL for aspirin, and 0.1625 to 0.4875 mg/mL for caffeine. The overall accuracy of the method ranged within 99 - 101% for the three drugs, and the instrumental and intermediate precision were demonstrated to be satisfactory. It can be suggested that the pharmacopoeial method of analysis can be used without the aid of internal standard, and the sample run time can be reduced, which will in turn save time of analysis and resources.

Automated summary

A combination of acetaminophen, caffeine, and aspirin in tablets is present in the US Pharmacopoeia. An optimized method of analysis for the simultaneous assay of the three analytes by HPLC without using the internal standard was developed, resulting in a shortened chromatogram runtime. The method is specific, linear, and accurate, allowing for the reduction of analysis time and resources.