ABSTRACT
A simple and sensitive stability-indicating HPLC-UV method was developed and validated for the determination of montelukast in the development of chewable tablet formulation. Chromatographic separation was achieved using Atlantis® T3 3µm C18 (4.6mmID X 10cm) analytical column. The mobile phase was consisted of KH2PO4 (0.05mM)-ACN-TEA (450:550:1.33, v/v/v) adjusted to pH 2.0 with orthophosphoric acid. The analysis was run at a flow rate of 1.5 mL/min with detection wavelength at 255nm. Method validation was performed in accordance with ICH guideline. Stress degradation studies, comprising of acid and alkali hydrolysis (1M HCl and 1M NaOH), oxidative degradation (3% H2O2), photo degradation and heat degradation, were performed. The standard calibration curve was linear from 0.0025 - 0.375mg/mL. The LOD and LLOQ were 0.01µg/mL and 0.04µg/mL. Stress degradation result shows that montelukast sodium was sensitive to photo degradation, oxidation and acid hydrolysis. Oxidative degradation kinetic study of montelukast sodium followed first order reaction, with r2 =0.9877, apparent degradation rate constant, k= 0.1066 h-1, t1/2= 6.6151 hr and t90% = 1.0118hr. In conclusion, HPLC-UV method was successfully developed and validated for determination of montelukast sodium in chewable tablet formulation.
Subject(s)
Acetates/chemistry , Chromatography, High Pressure Liquid/methods , Cyclopropanes/chemistry , Leukotriene Antagonists/chemistry , Quinolines/chemistry , Sulfides/chemistry , Drug Stability , Oxidation-Reduction , Tablets/chemistry , Ultraviolet RaysABSTRACT
Aim: To develop an LC-MS/MS method for simultaneous determination of duloxetine and its metabolite, 4-hydroxy duloxetine glucuronide (4HDG) in human plasma and to investigate the potential back-conversion of 4HDG to duloxetine using stability study. Materials & methods: The LC-MS/MS method was validated according to the EMA and USFDA Bioanalytical Method Validation Guidelines and applied to pilot bioequivalence study. Results & conclusion: The method validation results were within the acceptance limits. The stability study and incurred sample reanalysis results ruled out the occurrence of back-conversion. The study highlighted the conduct of back-conversion test and the advantages of LC-MS/MS method in terms of sensitivity, specificity and low consumption of organic solvents.
