Development and Validation of a Stability-Indicating RP-HPLC Method for Simultaneous Determination of Paracetamol, Tramadol HCl and Domperidone in a Combined Dosage Form

Abstract

Purpose: To develop a stability indicating RP-HPLC method for a combination drug product containing a high dose of paracetamol (PR) and low doses of domperidone (DM) and tramadol HCL (TR).Methods: The analytes are well separated by a reverse phase column and an isocratic mobile phase consisting of 0.1 %v/v trifluoroacetic acid: acetonitrile: methanol in the ratio 70:25:5 (v/v) with a flow rate of 1.0 mL/min. The effluent was monitored at 272 nm. The drug products were subjected to stress conditions of acid, base, peroxide, thermal and photolytic degradation and peak homogeneity of PR, TR and DM were obtained using photo diode array detector.Results: The degradation products were well resolved from PR, TR and DM peaks, thus indicating the stability-indicating nature of the method. The assay was linear from 165 – 495 μg/mL for PR, 18.75 – 56.25 μg/mL for TR, and 5 – 15 μg/mL for DM. Although the tablet contained high and low doses of the drugs, the intra- and inter-day variations were < 2.0 %.Conclusion: The proposed method was validated according to the ICH guidelines and proved suitable for stability and homogeneity testing, as well as for quality control of the combined drugs in pharmaceutical preparations.Keywords: HPLC, Isocratic, Peak purity, Simultaneous determination, Paracetamol, Tramadol, Domperidone