Simultaneous Quantitation of Theophylline and Guaifenesin in Syrup by HPLC, Derivative and Derivative Ratio Spectrophotometry for Quality Control Purposes

The aim of the present work was to develop a simple and rapid method for determination of theophylline (THP) and guaifenesin (GU) in syrup without involving any preparation operations like separation or masking. A HPLC and two spectrophotometric methods based on the derivation of the main spectra are described for the determination of THP and GU in combined pharmaceutical syrup form. The first derivative method can be applied only for THP and depends on the use of the second-order derivative spectra of the absorption spectrum of binary mixtures. The second derivative amplitudes at 291.6 nm were selected for the assay of THP. The second method is based on the use of the first derivative of the ratio-spectra obtained by dividing the absorption spectrum of binary mixtures by a standard spectrum of one of the compounds. The first derivative amplitudes at 286.3 and 231.7 nm were selected for the assay of THP and GU, respectively. Calibration curves were established at 5-40 mg/mL for GU and 20-70 mg/mL for THP. The proposed method was accurate with at least 99.5% recovery values and precise with coefficient of variation (CV) of 1.7% and 5.3% for THP and GU, respectively. Also a modified USP HPLC method was applied for determination of these two compounds in syrup. The results obtained by HPLC and derivative spectrophotometric methods applied to the same samples were compared together with selecting HPLC as a reference method for the developed spectrophotometric methods. The HPLC method was based on isocratic reversed-phase liquid chromatography by using C18 column with methanol: water (40:60, v/v) (pH 3.0) as mobile phase. Caffeine was used as an internal standard (IS) and the substances were detected at 280 nm. Calibration solutions used in HPLC were in the same range as spectrophotometric method and the detection and quantitation limits were found to be 6.9 and 20.1 mg/mL for THP and 3.7 and 11.1 mg/mL for GU, respectively. The proposed methods were successfully applied to the determination of the drugs in synthetic mixtures and commercially available syrup with a high recovery, good accuracy and precision.