The present part aims to develop and validate a simple, rapid, cost-effective, sensitive and extractive spectrophotometric methods for the determination of anti-depression drug; milnacipran HCl in pure form and pharmaceutical formulations. The developed methods are based on the formation of ion-pair complexes between milnacipran HCl with three dyes, namely, bromocresol purple (BCP), bromophenol blue (BPB), or methyl orange (MO) in acidic buffer solutions. Different factors affecting the reactions between milnacipran HCl and the dyes were studied and optimized. The formed complexes were extracted with methylene chloride and measured at 408, 413, and 423 nm using BCP, BPB and MO, respectively. The beer's law was obeyed in the ranges 1.0-14, 2.0-20 and 1.0-18 μg mL−1 for BCP, BPB and MO, respectively under the optimum conditions. The composition of the ion pairs was found 1:1. The molar absorptivity's, Sandell's sensitivity, limits of detection and the limits of quantification were calculated. Other method validation parameters, such as accuracy, intra-day and inter-day precision, robustness, ruggedness and selectivity, have been evaluated. The proposed methods have been applied successfully for the analysis of milnacipran HCl in p pure form and pharmaceutical formulations. The reliability of the methods was further ascertained by performing recovery studies using the standard addition method. Statistical comparison of the results with the reported method was performed by applying student's t- and F-tests and no significant statistical differences were obtained.