• P-ISSN2233-4203
  • E-ISSN2093-8950

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  • P-ISSN 2233-4203
  • E-ISSN 2093-8950

A Simple and Efficient Method to Determine Montelukast in Rat Plasma Using Liquid-Liquid Extraction and Tandem Mass Spectrometry

Mass Spectrometry Letters / Mass Spectrometry Letters, (P)2233-4203; (E)2093-8950
2020, v.11 no.4, pp.71-76
Kim Dong Yoon (Dankook University)
Lee Hyo Chun (Dankook University)
Jang Yong Jin (Dankook University)
Kim Jin Hee (Dankook University)
Lee Ha Ryeong (Dankook University)
Kang Myung Joo (Dankook University)
Choi Yong Seok (Dankook University)
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While montelukast (ML), a cysteinyl-leukotriene type 1 receptor (CysLT 1 ) antagonist is widely used to treat symp-toms of rhinitis or asthma, its formulations are mainly limited to solid preparation due to its instability. Recently, there have been attempts to develop various ML dosage forms, and this situation increases the demand of sensitive and creditable methods to determine ML in various samples such as plasma. Thus, here, a simple and efficient method to determine ML in rat plasma using liquid-liquid extraction (LLE) and multiple reaction monitoring was presented. The mixture of DCM:EtOAc (25:75, v/v), the optimized extract solvent for LLE was found to be effective to extract ML without hydrophilic salts and proteins from the sam-ple with limited volume. Also, the use of zafirlukast, instead of expensive ML-d 6 , as the internal standard makes the present method economical. The developed method was successfully validated in terms of selectivity, matrix effects (-14.8--6.9%), lin-earity (r 2 ³0.998 within 0.5-500 ng/mL), sensitivity (the limit of detection and the lower limit of quantitation, ≤0.5 ng/mL), accu-racy (88.4-100.6%), precision (3.0-13.3%), and recovery (80.8-86.3%) by following the FDA guidelines. Finally, the applicability of the validated method to pharmacokinetics (PK) studies was confirmed by the successful determination of PK parameters through it following oral administration of Singulair ® granule in rats. Therefore, the present method can contribute to the development of new ML formulations through its performance to determine ML in rat plasma efficiently and sensitively.

montelukast multiple reaction monitoring liquid-liquid extraction rat plasma pharmacokinetics

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Mass Spectrometry Letters