A simple and sensitive HPLC-MS/MS assay for the quantitation of montelukast in cell-based systems in vitro pulmonary drug permeability study.

Montelukast is a potent and selective antagonist of the cysteinyl leukotriene receptor 1 subtype (CysLT1) and widely used in the form of oral tablets and granules for asthma prophylaxis and treatment. Recently, due to the pulmonary inhaled administration can limit montelukast distribution in the systemic circulation, avoid the first-pass metabolism and have better therapeutic effects in respiratory disease treatment, explore alternative routes of administration, like delivery of montelukast via an inhaled, is a new research trend for montelukast. The aim of the current study was to develop and validate a simple, accurate, highly sensitive and selective liquid chromatography-tandem mass spectrometry method (LC-MS/MS) for determination of montelukast in an in vitro cell-based pulmonary pharmacokinetics system model, which can be used to be a better understanding the fate of inhaled montelukast in the lungs. In this study, montelukast was extracted by protein precipitation with acetonitrile containing labeled montelukast. The chromatography was performed on an Agilent Eclipse plus C8 column (4.6 mm × 100 mm, 3.5 µm, Darmstadt, Germany) operating at 35 ◦C. The mobile phase consisted of acetonitrile: 20 mM ammonium formate buffer (80: 20, v/v), was delivered at a flow rate of 0.5 mL/min. montelukast and the internal standard were both eluted at 4.2 min. A linear (1/x2) relationship was used to perform the calibration over an analytical range from 0.5 to 600 ng/mL. The intra- and inter-batch precision expressed as CV for four QC samples including LLOQ range from 1.14 % to 6.25 %. The intra- and inter-batch accuracy for four concentrations of montelukast were in the range of 95.19%-104.1%. All the values for accuracy and precision were within the acceptance range. The method met all the bioanalytical method validation requirements by ICH and was suitable for the assay of montelukast which in the in vitro cell-based pulmonary pharmacokinetics system model.

Reproductive parameters of female Macaca mulatta tcheliensis in the temperate forest of Mount Taihangshan, Jiyuan, China.

The remaining population of Macaca mulatta tcheliensis, approximately 3,000 individuals, is currently confined to the southern region of Mount Taihangshan, northern China. Using data collected from February 2003 to November 2012, we examined female reproductive characteristics in a seasonally food supplemented free-ranging group of M. m. tcheliensis (Wangwu 1, WW-1), inhabiting the Taishangshan Macaque National Nature Reserve (TMNNR), Jiyuan, China. We tested a series of predictions regarding the degree to which M. m. tcheliensis is best considered as a "strict income breeder," a "relaxed income breeder" or a "capital breeder." This group was comprised 18 adult females who produced 64 infants over the 10-year study period. In our study group (WW-1) adult female macaques gave birth to an average of 0.71 ± 0.26 infants per year. Infant mortality was 13.4 ± 19.3%. The age at first birth for mothers was 4.9 ± 0.5 years old. The mean inter-birth interval (IBI) was 15.4 ± 4.9 months. Based on the fact M. m. tcheliensis is a strictly seasonal breeder (76.6% of births occurred between April and May) with infants born during a time of the year when food availability appears to be high, and that their IBI is intermediate in length compared with other macaque populations, our results suggest that M. m. tcheliensis follows a birth pattern most consistent with a "relaxed income breeder" strategy.