Determination Of Montelukast Research Articles

STABILITY INDICATING ISOCRATIC HPLC APPROACH TO QUANTIFY MONTELUKAST AND BILASTINE MIX IN BULK AND TABLET FORMULATION

This paper describes an novel, rapid, simple, meticulous and unerring “stability indicating HPLC method” for the assessment of montelukast (MTT) and bilastine (BLE) mix in existence of their degradation products in tablet formulation. Zorbax column XDB-C18 was utilized to separate and analyse MTT and BLE mix. The isocratic mode elution of BLE and MTT mix was made with 0.1M disodium hydrogen phosphate buffer of pH 5.8 (55 % volume ratio) and methanol (45% volume ratio) at 1.0 mL min-1 flow stream. Strong linearity was recorded within the 2.5 - 20 µg mL-1 and 5 - 40 µg mL-1 concentration ranges, with coefficient determination values of 0.9994 and 0.9997, respectively, for MTT and BLE. The recovery percentiles of MTT and BLE were 99.593 % and 99.349 %, respectively. The precision displayed values less than 0.520 % for MTT and less than 0.745 % for BLE. The robustness too was shown in the chromatographic settings by minor variations. The specificity besides stability representing feature was evidenced since the degradation products arisen in stress situations did not interlope in the determination of MTT and BLE mix. Thus, this procedure can be applied for quality regulation analysis of BLE and MTT mix in formulations of tablets.

Determination of montelukast by new spectrophotometric method using bromocresol green

Determination of montelukast by new spectrophotometric method using bromocresol green

Development and Validation of Montelukast with Grape/Licorice Juices and its Application to Pharmacokinetic Studies by LC/MS

A simple, rapid and sensitive simultaneous method for validation and determination of Montelukast in rat plasma in the presence of grape and licorice juices has been done by using High Performance Liquid Chromatography–Mass Spectrometry (HPLC/MS). A mixture of (77.5 % methanol, 22.5 % of 0.2% FA in water) was used as a mobile phase, ACE 5 C8 column (50 X 2.1 mm, 5μ), and a flow rate of 0.1 ml/min were used, the auto-sampler injection volume was 5 microliters, and candesartan was used as an internal standard. According to the result obtained, the precision of predicted measurements for Montelukast was good (mean CV % 0.05) of grape on Montelukast Cmax (163.492 ng/ml ±113.27). Neither licorice gives significant decrease in the Montelukast Cmax (143.861ng/ml ±54.52), its only delay the average Montelukast Cmax to half an hour. Even for the AUC, there were no significant difference between Montelukast alone and Montelukast with grape, and Montelukast with licorice (P>0.05). The kinetic data shows that Montelukast plasma level was the same with both combination of Montelukast and grape, and Montelukast and licorice.

Development of an enantioselective capillary electrophoretic method for the simultaneous determination of montelukast enantiomeric and diastereoisomeric forms and its main degradation product.

A stereoselective CD-MEKC system has been developed for the quality control of Montelukast (MK), commercialized as a pure enantiomer. The proposed method is the first one that allows the simultaneous determination of MK, its enantiomeric form, diasteroisomers and its main degradation compound (MK sulphoxide). CD-MEKC system is composed of 10 mM SDS, 10 mM sulfobutylether-β-CD, 10 mM TM-β-CD, and 20 mM borate buffer at pH 9.0. Combination of these two CDs allows high baseline enantioresolution between MK and its enantiomeric impurity, but also, between the diasteroisomeric forms. Moreover, a multivariate design was applied to optimize operational parameters. The method was designed to meet with requirements of the official pharmacopoeias and fully validated according to international guidelines. Linearity of MK was demonstrated in the range from 10.0 to 100.0 μg/mL (r(2) = 0.9908) with a LOD and LOQ of 0.30 and 0.90 μg/mL, respectively. Intra and interday precision were evaluated and RSD values were below 2%, and also, accuracy expressed as percentage of recovery was in a range from 99.0 to 101.9 for the three assayed levels. The method allows determining 0.02% w/w of the enantiomeric and diasteroisomeric impurities, and 0.01% w/w of MK sulphoxide. Robustness was evaluated by a Plackett and Burman design. Finally, the CD-MEKC system was successfully applied to the determination of related substances in MK bulk drug and its quantification in two pediatric pharmaceutical dosage forms.

Bioequivalence Study of Two 10 mg Montelukast Immediate-Release Tablets Formulations: A Randomized, Single-Dose, Open-Label, Two Periods, Crossover Study

tablets in twenty-four healthy volunteers. The Test product was Montelukast* manufactured by Tecnoquimicas S.A. (Jamundi – Colombia) and the Reference product was Singulair® (Montelukast) made by Merck Sharp & Dohme Ltd. (Northumberland - United Kingdom). A crossover design 2 x 2 of single-dose, with two treatments, two periods, two sequences and with a washout period of one week was used. Blood samples were collected from 0, 5 to 24 hours after dosing. The determination of Montelukast in plasma was performed using a previously validated bio-analytical method of high-performance liquid chromatography with fluorescence detector (HPLC-FLD). Through Montelukast concentration curves versus time measured in the volunteers’ plasma, the pharmacokinetic parameters and bioequivalence were determined for both products. The pharmacokinetic parameters determined in this study for both the reference and test products were Cmax 440.6 ± 227.4 ng/ml, 460.5 ± 170.9 ng/ml, AUC0→∞ 3196.5 ± 1546.8 ng/h.ml, 3284.9 ± 1270.0 ng/h.ml and AUC0→24 3162.5 ± 1537.6 ng/h.ml, 3251.6 ± 1221.8 ng/h.ml respectively. For Montelukast, with a confidence interval of 90%, the ratio of the logarithmic transformation test product / reference product for AUC0→∞ was from 94.5 to 110.9 and the ratio test product/reference product for Cmax was from 89.0 to 110.4. These intervals are within the established bioequivalence range and therefore determined that the test formulation is interchangeable or bioequivalent to the reference.

Differential Pulse Voltammetric Determination of Montelukast in Tablets and Human Plasma by Using Chitosan Modified Carbon Paste Electrode

AbstractElectrochemical reduction and determination of montelukast (MKS) was studied in methanol – 0.1 M HCl solution (1 : 1, v/v) by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) at chitosan modified carbon paste electrode. The linear range was 1.70×10−7–1.83×10−5 M for DPV analysis. Limit of detection (LOD) and limit of quantification (LOQ) were 5.32×10−8 M and 1.61×10−7 M, respectively. The developed method was successfully applied to the determination of MKS in tablets and spiked human plasma. The results obtained were in good agreement with those obtained using a reported spectrofluorimetric technique.

Reliable and Precise Determination of Montelukast in Human Plasma by UPLC-MS/MS

A reliable, selective and precise ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/ MS) method is developed for the determination of montelukast in human plasma. The analyte and montelukast-d6 as an internal standard were extracted from plasma (100 µL) by liquid-liquid extraction. Chromatographic analysis was carried out on UPLC BEH C18 (50 mm × 2.1 mm, 1.7 µm) column under isocratic conditions using acetonitrile-3.0 mM ammonium formate, pH 4.0 adjusted with 0.1 % formic acid (90:10, v/v) as the mobile phase. For MS/MS quantitation in the positive ESI mode, the pre- cursor → product ion (m/z 586.1 → 422.1) transition was monitored for montelukast. The assay was linear in the concentration range of 0.05 - 200 ng/mL, while the chromatographic run time for the analysis was 1.2 min. The extraction recovery was within 95-98 % across four quality control samples. The precision (% coefficient of variation) and accuracy of the method ranged from 1.01 to 6.56 % and 97.2 to103.7 % respectively. Additionally, the method was validated for matrix effect, stability in plasma and whole blood and ruggedness. The method was efficiently used for a bioequivalence study of montelukast in 30 healthy subjects and the assay reproducibility was demonstrated by reanalysis of 131 incurred samples.

Novel LC Method Development and Validation for Simultaneous Determination of Montelukast and Doxofylline in Bulk and Pharmaceutical Dosage Forms

A novel rapid HPLC method was developed for simultaneous determination of montelukast and doxofylline in bulk and pharmaceutical dosage forms. Development of an analytical method for simultaneous estimation of drugs requires a lot of efforts and of course it is a challenging task. The method was developed by using C18 (150 mm × 4.6 mm, 5 μm) column; mobile phase consisting of methanol and phosphate buffer at pH 4.5; the flow rate of 1.0 mL/min and ultraviolet detection at 280 nm. Both drugs were sufficiently resolved having retention time of 4.7 min and 1.9 min for montelukast and doxofylline, respectively. The method was validated as per ICH Guidelines for various parameters like precision, linearity, accuracy, ruggedness, and robustness. The validated method was applied to the commercially available pharmaceutical dosage form and obtained the desired result.

Rapid Determination of Montelukast in Human Plasma by LC-ESI-MS/MS and Its Application to a Bioequivalence Study

A rapid liquid chromatography–electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the determination of montelukast in human plasma. The extraction of montelukast from plasma (300 µL) involved protein precipitation. Quantitation was performed using LC-ESI-MS/MS, operating in the positive ion and selective reaction monitoring (SRM) mode. The total chromatographic run time for the analysis was 1.5 min. A linear dynamic range was established from 5 to 800 ng mL−1 for montelukast. The method was fully validated especially with regard to real subject sample analysis. It was successfully applied to a bioequivalence study in 18 healthy human subjects under fed condition (human subjects were allowed to eat as per the prescribed diet for bioequivalence study).

Spectrophotometric method for quantitative determination of montelukast in bulk, pharmaceutical formulations and human serum

A simple ultraviolet spectrophotometric method for the estimation of montelukast in methanol has been devised and been compared with the existing pharmacopoeial RP-HPLC method for estimation of the drug. The limit of detection of montelukast at 283 nm was 75.2 ng/mL. The calibration was linear in the range of 3–45 μg/mL. Analytical parameters such as stability, selectivity, accuracy and precision have been established for the method in MONAKA® tablets and in human serum and evaluated statistically to assess the application of the method. The method was validated under the ICH and USP guidelines and found to comprise the advantages for simplicity, stability, sensitivity, reproducibility and accuracy for using as an alternate to the existing non-spectrophotometric methods for the routine analysis of the drug in pharmaceutical formulations and in pharmaceutical investigations involving montelukast.

Determination of montelukast (MK-0476) and its S-enantiomer in human plasma by stereoselective high-performance liquid chromatography with column-switching

A steoreoselective high-performance liquid chromatographic method was developed for the quantification of montelukast (free acid of Singulair™, or MK-0476), a potent and selective leukotriene D 4 (cysLT 1) recptor antagonist, and it S-enantiomer (L-768,232). The method involves protein precipitation and fluorescence detection. Chromatographic separation of the enantiomers from endogenous components in plasma and chiral resolution of the enantiomers are achieved by using column switching HPLC and an α-acid glycoprotein chiral column. The assay is linear in the range of 28.9–386 ng ml −1 of free acids of montelukast and L-768,232. The intraday precision (% relative standard deviation) values of this method were in the range of 2.5–9.1% for montelukast, and 2.4–6.8% for L-768,232, while the intraday accuracy values were in the range of 97–103% for montelukast and 96–104% for L-768,232. The interday precision values of this method at 48.2 and 193 ng ml −1 were 5.3 and 3.6%, respectively, for montelukast, and 4.2 and 3.7%, respectively, for L-768,232, while the interday accuracy values at these concentrations were 97 and 103%, respectively, for montelukast and 99 and 102%, respectively, for L-768,232. The utility of the methodology was demonstrated by analysis of plasma samples from a study in which healthy volunteers received 10 mg per day of montelukast orally for 7 days. Results of this study indicate that there is no apparent bioinversion of montelukast to its S-enantiomer in humans.