Development of greener and safer assays for hydrochloride drugs: photometric microtitration of phenylpropanolamine hydrochloride and metformin hydrochloride

An environmentally friendlier, safer and saver method is described for the assay of drugs as hydrochloride salts namely metformin hydrochloride and phenylpropanolamine hydrochloride via the determination of their chloride contents. In this method, an aqueous solution of drug was treated with measured excess of silver nitrate in the presence of nitric acid, followed by the determination of unreacted silver nitrate by Volhard's method using ammonium thiocyanate titrant and iron(III) alum indicator. To minimize the reagents consumed and wastes generated, the reactions were scaled down to less than 2 mL carried out in microcentrifuge tubes and using micropipettes for the transfer of reagents. The equivalence point was determined by spectrophotometry to diminish visual errors by reading the absorbance of red iron(III) thiocyante complex at 450 nm on microplates, which quickened the measurements of multi-samples. After validation, the method showed satisfactory accuracy and precision and was successfully applied for the assay of both drugs in raw materials, giving the results comparable to the pharmacopeial methods. In addition, the proposed assay was free from the use of harsh, toxic and environmentally harmful chemicals i.e. glacial acetic acid, acetic anhydride, mercuric acetate which are employed in the USP non-aqueous titration methods. Thus, it is considerably safer for analysts and is a cost-effective and green analytical method suitable for a sustainable environment.