Comparative validated chromatographic methods for the simultaneous determination of caffeine, codeine, paracetamol along with the related compound "p-aminophenol" in tablets

This paper presents two validated chromatographic methods, namely thin-layer chromatography (TLC)-densitometry and high-performance liquid chromatography (HPLC), for the simultaneous determination of caffeine (CAF), codeine (COD), paracetamol (PAR) in the presence of p-aminophenol (PAP) in their quaternary mixture. Good separation was achieved by using silica gel as the stationary phase and chloroform-methanol-acetone-ammonia (8:1:2:0.1, V/V) as the mobile phase in the case of TLC-densitometry with retardation factor (R-F) values of 0.38 +/- 0.02, 0.24 +/- 0.02, 0.61 +/- 0.02 and 0.46 +/- 0.02 for PAR, COD, CAF and PAP, respectively. Zorbax ODS column with mobile phase consisting of 0.1% orthophosphoric acid and acetonitrile (92:8, V/V) was used as stationary and mobile phase for HPLC, respectively, with retention time (t(R)) values of 1.1, 3.5, 4.6 and 8.5 min for CAF, PAP, COD and PAR, respectively. The two proposed methods were validated as per the International Council for Harmonisation guidelines. Finally, they were successfully applied for determination of the cited drugs in their quaternary mixture and marketed formulation.