Purpose: To develop and validate two innovative spectrophotometric methods used for the simultaneous determination of ambroxol hydrochloride and doxycycline in their binary mixture. 

Methods: Ratio subtraction and isoabsorptive point methods were used for the simultaneous determination of ambroxol hydrochloride and doxycycline in their binary mixture. Linear correlations were obtained in the concentration range of 6 - 40 and 4 - 32 µg mL^-1 for ambroxol hydrochloride and doxycycline, respectively. Ratio subtraction method was utilized for determination of ambroxol hydrochloride at 246.5 nm while isoabsorptive point method was employed for doxycycline at 244 nm (using methanol as a solvent) in mixtures as well as in their combined dosage form (Ambrodoxy capsules).

Results: The proposed methods were successfully applied to the analysis of the pharmaceutical capsules containing the two analytes. Recovery for ambroxol hydrochloride and doxycycline in capsules was 99.49 and 99.96 %, respectively. The relative standard deviation (% RSD) for the assay of the capsules was < 1 %. Validation of the two methods was assessed according to International Council on Harmonization (ICH) guidelines regarding linearity, accuracy, precision, specificity and range. The results of the proposed methods compared favorably with those obtained by a reported chemometrics-assisted ultraviolet (UV)-spectroscopic method.

Conclusion: The proposed methods are rapid, selective, simple and accurate. They also represent suitable alternatives to the chromatographic methods currently used for the analysis of the pharmaceutical mixtures in various dosage forms.