Determination of butamyrate citrate in cough preparations by derivative UV spectrophotometry and high performance liquid chromatography

Derivative spectrophotometric procedures and an isocratic high performance liquid chromatographic method for the determination of butamyrate citrate (Sinecod((R)), Safarol((R))) in cough syrups have been developed. In the spectrophotometric method, direct measurement of the drug at its absorption maxima is impossible because of interference from different absorbing excipients. Extraction of butamyrate citrate was performed with n-pentane/isopropyl alcohol. Quantification was carried out through the use of D-1 derivative at a trough depth of 253.6 nm where interferences from other coextracted compounds are negligible. The extraction efficiency expressed as a % recovery and precision were assessed by fortifying placebo syrup(s) with known amounts of the compound. Also, a reversed phase high performance liquid chromatographic method was used with a mobile phase containing 0.015 M aqueous tetraethylammonium hydrogen sulfate, methanol and acetonitrile 40:30:30 adjusted to pH 3.50 with ammonium hydroxide. The retention behavior of butamyrate citrate as a function of both pH and salt concentration in the aqueous portion of the mobile phase was investigated. Quantification was achieved with UV detection at 258 nm based on peak area. The HPLC method clearly separates the analyte from its degradation products derived after storage of samples under different stress conditions such as acid, alkaline, temperature, oxygen and light. The described methods were successfully applied to the determination of butamyrate citrate in commercial pharmaceutical products and in placebo syrups prepared in the laboratory with good accuracy and precision. The results of the present study show that the use of the derivatives and the HPLC procedure provide precise and sensitive methods for the determination of the compound in pharmaceutical formulations.