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.
Highlights
Montelukast, {1-[({(1R)-1-{3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl}-3-[2-(1-hydroxy-1methylethyl)phenyl]propyl}sulfanyl)methyl]cyclopropyl}acetic acid, has a molecular formula of C35H36ClNO3S and a molecular weight of 586.18 g/mol (Fig. 1a)
Standard stock solutions of MO were added to drug-free human plasma to obtain MO concentration levels of 1.00, 2.00, 5.00, 10.00, 50.00, 100.00, 200.00, 400.00, 600.00, and 800.00 ng mL−1 for analytical standards and 1.00, 3.00, 240.00, and 560.00 for quality control standards and stored in a −30°C set point freezer until analysis
The extraction recoveries of MO and MOD6 from human plasma were determined by analyzing quality control samples
Summary
Montelukast, {1-[({(1R)-1-{3-[(E)-2-(7-chloroquinolin-2-yl)ethenyl]phenyl}-3-[2-(1-hydroxy-1methylethyl)phenyl]propyl}sulfanyl)methyl]cyclopropyl}acetic acid, has a molecular formula of C35H36ClNO3S and a molecular weight of 586.18 g/mol (Fig. 1a). We have developed and validated the method over a concentration range of 1.0–800.0 ng mL−1 using 200μL plasma samples. This method was developed and validated as per FDA guidelines and was successfully employed in the analysis of plasma samples following oral administration of MO (5 mg) in healthy human volunteers [18].
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