Sensitive Titrimetric and Spectrophotometric Assay of Tramadol Hydrochloride in Pharmaceuticals using N-Bromosuccinimide and Indigocarmine as Reagents

摘要

Two indirect methods based on titrimetric and spectrophotometric techniques are described for the determination of tramadol hydrochloride (TDH) in bulk drug and in tablets using N-bromosuccinimide (NBS) and indigocarmine as reagents. In titrimetry, a measured excess of NBS is added to an acidified solution of TDH in the presence of potassium bromide and the unreacted NBS is determined iodometrically. Spectrophotometry involves the addition of a known excess of NBS to TDH in acid medium followed by estimation of residual NBS by reacting with a fixed amount of indigocarmine (IC) and measuring the absorbance at 610 nm. The working conditions of the methods have been optimized.Titrimetric procedure is applicable over the range 2.5-25.0 mg of TDH, and the reaction stoichiometry is found to be 1:1 (TDH: NBS). In the spectrophotometric method, the absorbance is found to increase linearly with the concentration of TDH, which is corroborated by the correlation coefficient of 0.9997 (n=8). The system obeys Beer's law in the range 0.75-15.0 μg ml~(-10 with an apparent molar absorptivity of 1.74 × 10~41 mol~(-1) cm~(-1) and Sandell sensitivity of 0.0172 μg cm~(-2). The limits of detection (LOD) and quantitation (LOQ) are calculated to be 0.11 and 0.34 μg ml~(-1), respectively. Within-day variation determined on three concentrations showed accuracies ranging from 0.20 to 3.35%. The RSD was determined to be < 3.45%. Day to day variation presented accuracies ranging from 0.67 to 3.60% with an RSD of <3.0%. The methods were successfully applied to the determination of TDH in tablet formulation and the results were compared with those of a reference method by applying Student's t-test and F-test. No interference was observed from common tablet adjuvants. The accuracy and reliability of the methods were further ascertained by recovery experiments via standard addition procedure.