Montelukast

Both Qualitative and Quantitative analysis plays a significant role in promising the safety and therapeutic efficacy of drugs in variety dosage forms. A bioanalytical method is a set of procedures involved in the collection, processing, storage, and analysis of a biological matrix for a chemical compound. Bioanalytical studies are employed to obtain a quantitative measure of the drug or its metabolites for the study of pharmacokinetics, toxicokinetic, bioequivalence and exposure-response like pharmacokinetic/ pharmacodynamic studies. Leukotriene receptor antagonists are widely used for the treatment and management of bronchial asthma and allergic rhinitis in different dosage forms. Drugs of this class are Zafirlukast, Montelukast and Pranlukast which are being potent drugs and are more than 99% bound to plasma proteins presenting special challenges in the development and validation of analytical methods from a variety of matrices. The main objective of this review is discussion on various analytical methods used, different solvents used as mobile phase and their retention times to understand final optimized chromatographic method which could be useful for the assessment of Pharmacokinetic parameters. Among different analytical methods, HPLC, LC-MS, UV-Visible spectroscopy and spectroflourimetric techniques are the most widely preferred techniques applied by the researchers worldwide. This review article gives information about various types of extraction procedures of the drug in plasma matrices to create an optimized method for method development and to offer practical approaches for determining validation parameters like specificity, selectivity, recovery, lower limit of quantitation (LOQ), limit of detection (LOD), linearity, range, accuracy, precision, stability, ruggedness and robustness of High performance liquid chromatographic methods (HPLC)  to support pharmacokinetic studies. Accurate and sensitive analytical methods for quantitation of drugs and their metabolites are very important for the successful conduct of preclinical and clinical pharmacology studies..

In the present paper, the authors described a novel Liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the determination of montelukast in human plasma using montelukast d6 as internal standard (IS). After solid phase extraction (SPE), the analyte and the IS were chromatographed on a C18 columns using a isocratic mobile phase composed of acetonitrile–5mM ammonium acetate (80:20, v/v) pumped at a flow rate of 0.8mL/min. The proposed method was validated in the range of 5.01–599.91 ng/mL as per the US FDA guidelines. Precision and accuracy results were calculated using five successful calibration curves. Analyte stability in true samples and in plasma samples under different conditions were established and results met the acceptance criteria. The chromatographic run time was set at 3 min, which makes the proposed method is high through put. The method was successfully applied to a pharmacokinetic study in healthy South Indian male subjects under fasting condition.

A new RP – HPLC method was developed for the simultaneous determination of  Montelukast and Rupatadine fumerate in combined dosage form. An Inertsil C18 column(100 x 4.6, 5µm) was used with mobile phase of composition Methanol : Buffer(0.1% triethyl amine in water with pH adjusted to 3.0 (70:30v/v at pH 4.6) at a flow rate of 1.0 mL/min and injection volume of 20µL with UV detection at 266 nm for separating Montelukast and Rupatadine fumerate. The retention time of Rupatadine fumerate and Montelukast were 5.76 min and 2.86 min respectively. The runtime of the analysis was 6 minutes. The specificity, linearity, precision, accuracy, limit of detection (LOD), limit of quantification (LOQ), ruggedness and robustness of the developed method were studied to validate as per ICH guidelines. The Linearity range for Montelukast and Rupatadine fumerate were 5.0 – 30.0 µg/ml and 5.0 – 30.0 µg/ml, respectively. The percentage recoveries were in the range for Montelukast and Rupatadine fumerate98.80-100.11 % and 99.06-99.44 %, respectively. The developed  method could be used for routine analysis of Montelukast and Rupatadine fumeratein their combined dosage forms.