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, pho- tolysis 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.
Highlights
Milnacipran is an anti-depressant drug, chemically as [2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide] hydrochloride and its structural formula is C15H22N2O·HCl
The determination was done for active pharmaceutical ingredient and its pharmaceutical dosage forms in the presence of degradation products, and its process-related impurities
Fibromyalgia syndrome (FMS) is a complex syndrome characterized by chronic widespread muscular pain associated with other symptoms such as fatigue, cognitive dysfunction, sleep disturbance, depression, anxiety, and stiffness
Summary
Milnacipran is an anti-depressant drug, chemically as [2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide] hydrochloride and its structural formula is C15H22N2O·HCl. In January 2009, Milnacipran (under the brand name Savella) has been approved only for the treatment of fibromyalgia by the Food and Drug Administration (FDA) in the United States for the management of adult FMS patients. Milnacipran has proven efficacy in managing global FMS symptoms and pain as well as diminishing symptoms of fatigue and cognitive dysfunction without affecting sleep. Due to its antidepressant activity, Milnacipran can be beneficial to FMS patients with coexisting depression. Inhibition of both neurotransmitters works synergistically to treat both FMS as well as depression [1,2,3,4,5,6,7]
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