Validated spectrophotometric methods for determination of sodium valproate based on charge transfer complexation reactions

•For the first time, charge transfer complexation reactions of sodium valproate have been investigated.•The proposed methods were applied for analysis of sodium valproate dosage forms without interference from the excipients.•The proposed methods are simple, direct, economic and advantageous to the reported methods of analysis of sodium valproate.

This work presents the development, validation and application of four simple and direct spectrophotometric methods for determination of sodium valproate (VP) through charge transfer complexation reactions. The first method is based on the reaction of the drug with p-chloranilic acid (p-CA) in acetone to give a purple colored product with maximum absorbance at 524 nm. The second method depends on the reaction of VP with dichlone (DC) in dimethylformamide forming a reddish orange product measured at 490 nm. The third method is based upon the interaction of VP and picric acid (PA) in chloroform resulting in the formation of a yellow complex measured at 415 nm. The fourth method involves the formation of a yellow complex peaking at 361 nm upon the reaction of the drug with iodine in chloroform. Experimental conditions affecting the color development were studied and optimized. Stoichiometry of the reactions was determined. The proposed spectrophotometric procedures were effectively validated with respect to linearity, ranges, precision, accuracy, specificity, robustness, detection and quantification limits. Calibration curves of the formed color products with p-CA, DC, PA and iodine showed good linear relationships over the concentration ranges 24–144, 40–200, 2–20 and 1–8 μg/mL respectively. The proposed methods were successfully applied to the assay of sodium valproate in tablets and oral solution dosage forms with good accuracy and precision. Assay results were statistically compared to a reference pharmacopoeial HPLC method where no significant differences were observed between the proposed methods and reference method.

Graphical abstract.Absorption spectra of the CT complexes of VP with p-CA (1), DC (2), PA (3) and iodine (4).Figure optionsDownload full-size imageDownload as PowerPoint slide