Method Development and Validation of Montelukast in Human Plasma by HPLC Coupled with ESI-MS/MS: Application to a Bioequivalence Study

Abstract

A simple, sensitive, and specific LC-ESI–MS/MS method for quantification of Montelukast (MO) in human plasma using Montelukast-d6 (MOD6) as an internal standard (IS) is discussed here. Chromatographic separation was performed on YMC-pack pro C18, 50 x 4.6 mm, S-3 μm column with an isocratic mobile phase composed of 10mM ammonium formate (pH 4.0):acetonitrile (20:80 v/v), at a flow-rate of 0.8 mL min−1. MO and MOD6 were detected with proton adducts at m/z 586.2→568.2 and 592.3→574.2 in multiple reaction monitoring (MRM) positive mode respectively. MO and MOD6 were extracted using acetonitrile as precipitating agent. The method was validated over a linear concentration range of 1.0–800.0 ng mL−1 with correlation coefficient (r2) ≥ 0.9996. The intraday precision and accuracy were within 1.91–7.10 and 98.32–99.17. The inter-day precision and accuracy were within 3.42–4.41% and 98.14–99.27% for MO. Both analytes were found to be stable throughout three freeze-thawing cycles, bench top, and autosampler stability studies. This method was utilized successfully for the analysis of plasma samples following oral administration of MO (5 mg) in 31 healthy Indian male human volunteers under fasting conditions.

Pharmacokinetic Analysis of Montelukast in Healthy Korean Volunteers by High Performance Liquid Chromatography-Tandem Mass Spectrometry

“…These methods include chromatographic assay (Amin et al, 1995;Liu et al, 1997; AlRawithi 2001), usage of dual column (Smith et al, 2004), column switching (Ochiai et al, 1998), spectrofluorometry (Alsarra et al, 2005) or mass spectrometry (Challa et al, 2010;Sripalakit et al, 2008). However, most of these methods required laborious sample pretreatment or derivatization, and long chromatographic run times, and thus, are not convenient for analyzing the large numbers of samples generated during pharmacokinetic research.…”

“…The observed mean maximum plasma concentration (C max ) was 670.3 ± 149.8 ng/mL, mean T max was 2.7 ± 1.0 hr, and the half-life of montelukast during the terminal phase (T 1/2 ) was 5.5 ± 1.1 hr (Table II). Pharmacokinetic studies of montelukast have been reported in healthy human (Challa BR et al, 2010;Sripalakit P et al, 2008;Cheng H et al, 1996;Bharathi DV et al, 2009). Among the data, pharmacokinetic parameters are shown to similar property considering different administration dose.…”

A Novel Simple Method for Resolving Overlapped Spectral Data with A Wide Range of Applicability, and Its Application as a Stability Indicating Method for Determination of Tazarotene

“…Several manipulations were performed on the raw overlapping spectral data to enable mixture resolution for example, using different order derivatives [1][2][3][4][5][6], derivatives of the ratio spectrum [7][8][9] and ratio subtraction technique [10].…”

Development and validation of RP-HPLC method with ultraviolet detection for estimation of montelukast in rabbit plasma: Application to preclinical pharmacokinetics

“…1 A review of literature reveals that number of analytical and bioanalytical methods have been published for quantification of MKS. As long as bioanalysis of MKS is concerned there are great deal of methods ranging from voltammetry 2 to LC-MS/MS assays 3,4 have been reported. Amongst all reported bioanalysis assay methods, HPLC analysis with fluorescence detection 5,6,7 has been tried by many authors by various modifications either in instrumentation part or in sample preparation part.…”