A Stability Indicating U-HPLC Method for Milnacipran in Bulk Drugs and Pharmaceutical Dosage Forms

Abstract

The objective of the current study was to develop a validated, specific and stability-indicating reverse phase UHPLC method for the quantitative determination of Milnacipran and its related substances. The determination was done for active pharmaceutical ingredient and its pharmaceutical dosage forms in the presence of degradation products, and its process-related impurities. The drug was subjected to stress conditions of hydrolysis (acid and base), oxidation, photolysis and thermal degradation per International Conference on Harmonization (ICH) prescribed stress conditions to show the stability-indicating power of the method. Significant degradation was observed during acid, base, oxidative and neutral stress hydrolysis. The chromatographic conditions were optimized using an impurity-spiked solution and the samples generated from forced degradation studies. In the developed UHPLC method, the resolution between Milnacipran and its process-related impurities was found to be greater than 2.0. Regression analysis shows an r value (correlation coefficient) of greater than 0.999 for Milnacipran and it's all the five impurities. The chromatographic separation was achieved on a C18 stationary phase. The method employed a linear gradient elution and the detection wavelength was set at 220 nm. The mobile phase consists of buffer and acetonitrile delivered at a flow rate of 0.2 mL·min -1 . Buffer consists a mixture of 10 mM Sodium dihydrogen phosphate monohydrate and 10 mM hexane sulfonate sodium salt, pH adjusted to 2.5 using ortho phosphoric acid. The mobile phase A consists of buffer and acetonitrile (950:50, v/v) and mobile phase B consists of acetonitrile. The stress samples were assayed against a qualified reference standard and the mass balance was found to be close to 99.5%. The developed RP-LC method was validated with respect to linearity, accuracy, precision and robustness.

Stability-Indicating Spectrophotometric Methods for Determination of Milnacipran HCl and Duloxetine HCl in Bulk Drug and Pharmaceutical Formulations

“…Major Pharmacopeias like USP, EP, and BP have not reported spectrophotometric methods for the determination of Milnacipran HCl and Duloxetine HCl. Some sophisticated analytical methods for estimation of Milnacipran HCl [6][7][8][9][10][11][12][13] and Duloxetine HCl [14][15][16][17][18] were stated in the literature. However, there hasn't been a stability-indicating spectrophotometric method yet developed for their determination in bulk and pharmaceutical formulations.…”

Liquid chromatography/electrospray ionization tandem mass spectrometric study of milnacipran and its stressed degradation products

“…[7] Recently, a stabilityindicating ultra-performance liquid chromatography (UPLC) method for MIL has been reported. [8] However, no information exists in the literature on the degradation behavior and stability indicating an LC/MS method of MIL. Hence, the present study focuses on the identification and structural characterization of the degradation products of MIL by using LC/MS/MS and accurate mass measurements.…”