Extraction-free spectrophotometric assay of the antitussive drug pentoxyverine citrate using sulfonephthalein dyes

Pentoxyverine citrate (PEN-citrate) is an antitussive (cough suppressant) drug used for cough associated with illnesses like common cold. In this work, PEN-citrate is quantified by applying a simple, direct and accurate spectrophotometric method in pure form, pharmaceutical formulation (Cabella®, 2.13 mg/mL) and human serum samples. The formation of a stable yellow ion-pair with sulfonephthalein dyes; bromocresol green (BCG), bromophenol blue (BPB), bromothymol blue (BTB), bromocresol purple (BCP), bromochlorophenol blue (BChPB) and bromoxylenol blue (BXB), in three nonpolar solvents (chloroform, dichloromethane, acetonitrile) is used as the basis for this method. This is the first assay method reported for the quantification of PEN-citrate using the sulfonephthaleins as coloring agents. Diverse parameters were investigated in order to optimize the calibration curve conditions. The strategy was validated with respect to linearity range, precision, accuracy, specificity, robustness and limits of detection (LOD) and quantification (LOQ). In addition, solvents of different polarities were utilized to investigate the color reaction, LIGHT absorption and to allow for increasing the method sensitivity. Beer's law is obeyed over a wide concentration range (up to 42.05 μg/mL in case of BTB method). LOD and LOQ values reached 0.22 and 0.72 μg/mL, respectively, upon using BChPB. The relative standard deviation (%RSD) was ≤1.91% while correlation coefficient values (r) were ≥ 0.9974. High molar absorptivity values and low values of Sandell's sensitivity were obtained indicating that the proposed methods are highly sensitive. The validated methods were applied to the analysis of PEN-citrate in the dosage form and human serum samples where the drug was successfully resolved from the pharmaceutical additives and serum components with recoveries ≥98.98%.