ABSTRACT
Accurate, precise, and sensitive LC-MS/MS assay method for the determination of montelukast (MO) in human plasma samples using gliclazide (GL) as internal standard was developed and applied in pharmacokinetics study.MO extracted by protein precipitation using acetonitrile. Chromatographic separation was carried out using a Agilant Triple quadrupoles mass spectrometer with API source with an Agilant SB- C18 (50×4.6 mm), 1.8 µm particle size column. A mobile phase consisting of acetonitrile: 0.1% formic acid (84:16) was delivered. Calibration curves were linear in the concentration range of (10.00-800.00) ng/ml. The bioanalytical method for determination of MO was successfully applied to assess pharmacokinetics of montelukast. The LLOQ was sensitive enough for detecting terminal phase concentrations of the drug. This study showed that developed method is suitable for MO pharmacokinetic study.
Subject(s)
Acetates/pharmacokinetics , Chromatography, Liquid/methods , Leukotriene Antagonists/pharmacokinetics , Quinolines/pharmacokinetics , Tandem Mass Spectrometry/methods , Acetates/adverse effects , Adult , Cyclopropanes , Humans , Male , Quinolines/adverse effects , SulfidesABSTRACT
Zafirlukast is a selective leukotriene receptor antagonist used for the prophylaxis and chronic treatment of asthma. The aim of the present study was to develop a simple sensitive ultra-performance liquid chromatography tandem mass spectroscopy method for rapid determination of zafirlukast in plasma. After a simple one step protein precipitation by acetonitrile, zafirlukast and montelukast (IS) were separated on Acquity UPLC BEH(TM) C18 column (50 × 2.1 mm, i.d. 1.7 µm, Waters, USA) using a mobile phase of acetonitrile:water containing 10 mM acetic acid (80:20, v/v) at a flow rate of 0.3 mL/min. Zafirlukast and IS were eluted at 0.51 and 1.1 min, respectively with a total run time of only 1.5 min. The mass spectrometric determination was carried out using an electrospray interface operated in the negative mode with multiple reactions monitoring mode. The precursor to product ion transitions of m/z 574.11>462.07 and m/z 584.2>472.1 were used to quantify zafirlukast and IS, respectively. The method was linear in the concentration range of 0.17-600 ng/mL with coefficients of determination greater than 0.996 and lower limit of quantitation of 0.17 ng/mL. Intra-day and inter-day accuracies were 88.3-113.9% and the precisions were ≤ 12.6%. Zafirlukast was found to stable under various storage and sample processing conditions as per guidelines of bio-analytical method validation. The method developed herein is simple and rapid, and was successfully applied for the pharmacokinetic study in rabbits.
Subject(s)
Leukotriene Antagonists/blood , Leukotriene Antagonists/pharmacokinetics , Tosyl Compounds/blood , Tosyl Compounds/pharmacokinetics , Animals , Calibration , Chromatography, High Pressure Liquid , Indicators and Reagents , Indoles , Male , Phenylcarbamates , Quality Control , Rabbits , Reproducibility of Results , Sulfonamides , Tandem Mass SpectrometryABSTRACT
The effect of protein malnutrition (PM) on the embryotoxicity and teratogenicity of aspirin in rats has been studied. Protein malnourishment was produced from Days 7 to 21 of gestation by limiting the casein content of the diet to 5% in comparison to 20% for the normal animals. Six dose levels of aspirin (50-175 mg kg-1) were administered p.o. from Days 8 to 11 of pregnancy. Aspirin from 75 mg kg-1 d-1 induced growth retardation, embryolethality and teratogenicity, as shown by external, skeletal and visceral malformations. All these effects were potentiated by protein malnutrition.
