Chemometric-assisted RP-HPLC method for the simultaneous determination of ambroxol hydrochloride, terbutaline sulfate, and guaiphenesin in combined dosage form

ABSTRACT

An isocratic reverse-phase High performance liquid chromatography (HPLC) method using a chemometric modelwas developed and validated for the simultaneous determination of ambroxol hydrochloride, terbutaline sulfate,and guaiphenesin in their combined dosage form. Central composite design which is a subset of response surfacemethodology was used as the chemometric model. The separation of three drugs was carried out by using a PhenomenexC18 column and detection at 220 nm using a UV detector. Based on initial trials, the three factors selected for thedesign were methanol (MN) concentration, mobile phase pH, and flow rate in the range of 55%–65% (v/v), 4–5 units,and 0.6–1 ml/min, respectively. The impact of the selected factors on the responses like retention time of first peak(tR1), resolution of 2nd and 3rd peak (Rs2,3), and theoretical plates of the first peak (TP1) were evaluated. Derringers’desirability function was used to optimize the responses. The conditions which were optimized for the assay of drugswere MN, ACN, and 50 mM KH2PO4 (pH 5) in the ratio of 551035 at a flow rate of 0.8 ml/minute. The developedand optimized method was validated as per the International conference on harmonization (ICH) guidelines and canbe used for routine analysis in quality control laboratories.