A Validated LC Method for Determination of the Enantiomeric Purity of Montelukast Sodium in Bulk Drug Samples and Pharmaceutical Dosage Forms

Simultaneous Determination of Montelukast Sodium S-Enantiomer and A5 Enantiomers in Montelukast Sodium Bulk Drug by Normal-Phase Chiral HPLC

“…6.1, 2.6 and 2.2 ng, respectively. The LOD was 2.4 ng and the LOQ was 6.1 ng for montelukast sodium S-enantiomer, comparing with the method reported by Radhakrishnan et al (LOD was 70 ng and LOQ was 200 ng for montelukast sodium S-enantiomer) [24] , the LOD was improved approximately 30 times and the LOQ increased by 30 times. The reason accounted for sensitivity increase may be that the mobile phase with dioxane has a more intensive UV background absorption than that of without it that led to a poor light transmittance and reduced the detective sensitivity.…”

“…Compared with the methods reported, the proposed method in this paper has a better sensitivity with LOD of 2.4 ng for montelukast S-enantiomer than that reported by Radhakrishnan et al [24] , the latter was 70 ng. Compared with the report by Liu [22] , the proposed method can save test cost due to using a more durable chiral column than that used by Liu, which stationary phase was α-acid glycoprotein easily damaged by various organic reagents [23] .…”

“…N-hexane-ethanol-1,4-dioxane-TFA-DEA system was taken as eluent for separation of montelukast sodium enantiomers, that has been reported by Radhakrishnan et al [24] but, in view of the property of eluent, only the chiral column with bonded stationary phase can be used, that has restricted the use of that with coated stationary phase in determination of montelukast enantiomers. For the reason mentioned above, in this paper, n-hexane, ethanol and isopropanol were screened as candidates for composition of mobile phase, and because of alkalinity of montelukast sodium, a proper amount of DEA or TFA could be added for improvement of stereoselectivity.…”

“…However, in EP 8.0, the injection concentration was 1000 μg/ml，which is more than the maximum concentration of 100 μg/ml, undoubtedly, it may seriously destroy the column. Radhakrishnan et al [24] developed a chiral high performance liquid chromatography (HPLC) method for determination of montelukast S-enantiomer in montelukast sodium on a chiral pak-IA column with an eluent of n-hexane:ethanol:1,4-dioxane:trifluoroacetic acid (TFA):diethylamine (DEA) (65:25:10:0.3:0.05, v/v/ v/v/v), but its sensitivity was poor with the limit of quantitation (LOQ) of 200 ng, it accounted for 2% of quality of montelukast sodium sample (1000 μg/ml of montelukast sodium and 10 μl injection volume), which does not meet the requirement of montelukast sodium quality criteria in EP 8.0. In addition, as process impurities, the contents of both A5 and A5 R-enantiomer should be strictly limited, however, up to now, there is not a method to be reported for determination of A5 and its enantiomer.…”

Isolation and Characterization of S-Enantiomer in Montelukast

“…It binds to the human CysLT1 receptor with an IC 50 of less than 5 nm with no appreciable binding to the CysLT2 receptor. Few HPLC methods are there for the determination of Montelukast sodium were reported in literatures [5,6]. The (S)-enantiomer is the undesired which can be present as a chiral impurity without any pharmacological and toxicological reports by now.…”