•HPTLC and stability-indicating HPLC methods were developed for the simultaneous analysis of DXT and MNT

•DXT and MNT were separated in presence of their degradation products

•All methods were validated according to ICH Guidelines.

•All methods were successfully applied for analysis of lozenges containing both drugs.

•First analysis of MNT as an active ingredient in lozenges.

Two chromatographic methods were developed for the assay of the FDA approved lozenges containing dextromethorphan hydrobromide (DXT) and menthol (MNT). The first was a green HPTLC method which uses a mobile phase of methanol-ammonia (10:0.1, v/v). The densitometric measurements of the spots which were retained at 0.28 ± 0.01 for DXT and 0.76 ± 0.02 for MNT was done at 210 nm. The other method was RP-HPLC method with stability indicating merits at which a mixture of 20 mM phosphate buffer pH 3 and acetonitrile as mobile phase in isocratic mode was used. The cited drugs were resolved in RP-HPLC method using isocratic elution using 20 mM phosphate buffer: acetonitrile (65:35 v/v) with retention times of 2.21 and 3.47 min for MNT and DXT, respectively and quantified using 215 nm. Both methods were entirely validated and both methods were successfully able to analyze both drugs in presence of lozenges inactive ingredients. HPLC method had the advantage of being stability indicating at which resolution of the drugs from their forced degradation products was successfully attained. For HPTLC method, both drugs showed reasonable R_F values when compared to rapidly eluted MNT in RP-HPLC; also it was more environmentally friendly than RP-HPLC as it used solvents which are less toxic and greener.