A rapid, specific, sensitive, and precise reverse-phase UPLC method developed for the quantitative determination of an atypical antipsychotic drug Iloperidone and its eight potential impurities in drug substances and ...A rapid, specific, sensitive, and precise reverse-phase UPLC method developed for the quantitative determination of an atypical antipsychotic drug Iloperidone and its eight potential impurities in drug substances and drug products is described in this report. Chromatographic separation was achieved on a Waters Acquity UPLC®HSS C18 (2.1 mm × 100 mm, 1.8 micron) column thermostated at 35°C with a short runtime of 10 min. Quantification is achieved with photodiode array detection at 225 nm over the concentration range of 0.03 - 0.15 μg/mL. Forced degradation study was carried out under acidic, alkaline, oxidative, photolytic and thermal conditions to demonstrate the stability-indicating capability of the developed UPLC method. Comparison of system performance with conventional high-performance liquid chromatography is made with respect to analysis time, efficiency, and sensitivity. The method is validated according to the ICH guidelines and is applied successfully for the determination of Iloperidone in tablets.展开更多
Objective: To determine the impact of iloperidone treatment on metabolic parameters. Methods: Data were analyzed from 3210 patients who received iloperidone and 587 patients who received placebo for up to 2 years duri...Objective: To determine the impact of iloperidone treatment on metabolic parameters. Methods: Data were analyzed from 3210 patients who received iloperidone and 587 patients who received placebo for up to 2 years during 9 Phase II and Phase III studies (integrated safety database). Patients were pooled by most frequent iloperidone dose into 3 groups: 4 - 8 mg/d, 10 - 16 mg/d, and 20 - 24 mg/d. Laboratory data from 8 studies were random (fasting and nonfasting) while patients from 1 study (n = 447) were all sampled at fasting. Results: Mean (standard deviation [SD]) weight gain from baseline to endpoint was 2.1 (6.8) kg for all patients on iloperidone. Fasting mean (SD) total cholesterol changes from baseline to end of study were 8.2 (31.6) for iloperidone and -2.2 (35.2) mg/dL for placebo. Fasting mean (SD) triglyceride changes during this period were iloperidone: -0.83 (82.3);placebo: 16.5 (113.1) mg/dL. Fasting mean (SD) glucose changes were iloperidone: 6.6 (24.0);placebo: -0.05 (17.0) mg/dL from baseline to end of study. Glycosylated hemoglobin levels were unchanged following iloperidone treatment. Conclusion: These data suggest a metabolic profile for iloperidone of modest weight gain accompanied by small changes in lipids and glucose that are unlikely to be of clinical concern.展开更多
文摘A rapid, specific, sensitive, and precise reverse-phase UPLC method developed for the quantitative determination of an atypical antipsychotic drug Iloperidone and its eight potential impurities in drug substances and drug products is described in this report. Chromatographic separation was achieved on a Waters Acquity UPLC®HSS C18 (2.1 mm × 100 mm, 1.8 micron) column thermostated at 35°C with a short runtime of 10 min. Quantification is achieved with photodiode array detection at 225 nm over the concentration range of 0.03 - 0.15 μg/mL. Forced degradation study was carried out under acidic, alkaline, oxidative, photolytic and thermal conditions to demonstrate the stability-indicating capability of the developed UPLC method. Comparison of system performance with conventional high-performance liquid chromatography is made with respect to analysis time, efficiency, and sensitivity. The method is validated according to the ICH guidelines and is applied successfully for the determination of Iloperidone in tablets.
文摘Objective: To determine the impact of iloperidone treatment on metabolic parameters. Methods: Data were analyzed from 3210 patients who received iloperidone and 587 patients who received placebo for up to 2 years during 9 Phase II and Phase III studies (integrated safety database). Patients were pooled by most frequent iloperidone dose into 3 groups: 4 - 8 mg/d, 10 - 16 mg/d, and 20 - 24 mg/d. Laboratory data from 8 studies were random (fasting and nonfasting) while patients from 1 study (n = 447) were all sampled at fasting. Results: Mean (standard deviation [SD]) weight gain from baseline to endpoint was 2.1 (6.8) kg for all patients on iloperidone. Fasting mean (SD) total cholesterol changes from baseline to end of study were 8.2 (31.6) for iloperidone and -2.2 (35.2) mg/dL for placebo. Fasting mean (SD) triglyceride changes during this period were iloperidone: -0.83 (82.3);placebo: 16.5 (113.1) mg/dL. Fasting mean (SD) glucose changes were iloperidone: 6.6 (24.0);placebo: -0.05 (17.0) mg/dL from baseline to end of study. Glycosylated hemoglobin levels were unchanged following iloperidone treatment. Conclusion: These data suggest a metabolic profile for iloperidone of modest weight gain accompanied by small changes in lipids and glucose that are unlikely to be of clinical concern.
