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 determinati...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.展开更多
Background: Among neurotransmitter influencing memory formation, the noradrenergic system has been recognized as an important system. Memory formation involves various regions including the prefrontal cortex, hippocam...Background: Among neurotransmitter influencing memory formation, the noradrenergic system has been recognized as an important system. Memory formation involves various regions including the prefrontal cortex, hippocampus, amygdala and septum. Method: We investigated the effects of milnacipran on passive avoidance task and evaluated Fos counting in the prefrontal cortex, hippocampus, septum, amygdala and nucleus accumbens. Results: The milnacipran-treated rats (20 mg/kg, 4 days) showed a significant decrease in the number of Fos-immunoreactive cells in the infralimbic portion of prefrontal cortex, the shell portion of nucleus accumbens and the CA1 region of hippocampus, but a significant increase in the Fos counts in the lateral septum with no changes in the Fos counts in the striatum and amygdala. The milnacipran-treated rats showed amelioration in memory extinction (although not statistically significant), but not in memory acquisition and consolidation in the passive avoidance test. Conclusion: The differential activation of the brain regions might be possible sites for ameliorating memory extinction as well as antidepressant effects.展开更多
The efficacy of milnacipran for the treatment of ADHD symptoms in adult Asperger’s disorder patients was examined. Fifteen consecutive adult Asperger’s disorder patients with ADHD symptoms were treated with milnacip...The efficacy of milnacipran for the treatment of ADHD symptoms in adult Asperger’s disorder patients was examined. Fifteen consecutive adult Asperger’s disorder patients with ADHD symptoms were treated with milnacipran for 8 weeks. Global Assessment of Functioning (GAF) and Conners’ Adult ADHD Rating Scales Objective Screening Version (CAARS-O-SV) were used for the assessment. The mean GAF scores in the 15 patients improved significantly. Inattention, inattention + hyperactivity/impulsivity and ADHD index in CAARS-O-SV were also significantly improved. Milnacipran might be useful for ADHD symptoms, exerting its effects by increasing serotonin and noradrenaline activities in Asperger’s disorder.展开更多
文摘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.
文摘Background: Among neurotransmitter influencing memory formation, the noradrenergic system has been recognized as an important system. Memory formation involves various regions including the prefrontal cortex, hippocampus, amygdala and septum. Method: We investigated the effects of milnacipran on passive avoidance task and evaluated Fos counting in the prefrontal cortex, hippocampus, septum, amygdala and nucleus accumbens. Results: The milnacipran-treated rats (20 mg/kg, 4 days) showed a significant decrease in the number of Fos-immunoreactive cells in the infralimbic portion of prefrontal cortex, the shell portion of nucleus accumbens and the CA1 region of hippocampus, but a significant increase in the Fos counts in the lateral septum with no changes in the Fos counts in the striatum and amygdala. The milnacipran-treated rats showed amelioration in memory extinction (although not statistically significant), but not in memory acquisition and consolidation in the passive avoidance test. Conclusion: The differential activation of the brain regions might be possible sites for ameliorating memory extinction as well as antidepressant effects.
文摘The efficacy of milnacipran for the treatment of ADHD symptoms in adult Asperger’s disorder patients was examined. Fifteen consecutive adult Asperger’s disorder patients with ADHD symptoms were treated with milnacipran for 8 weeks. Global Assessment of Functioning (GAF) and Conners’ Adult ADHD Rating Scales Objective Screening Version (CAARS-O-SV) were used for the assessment. The mean GAF scores in the 15 patients improved significantly. Inattention, inattention + hyperactivity/impulsivity and ADHD index in CAARS-O-SV were also significantly improved. Milnacipran might be useful for ADHD symptoms, exerting its effects by increasing serotonin and noradrenaline activities in Asperger’s disorder.
