Pharmacognosy and Pharmaceutical Chemistry Department, Faculty of Pharmacy, Taibah University, Al Madinah Almunawarah 30001, Saudi Arabia.
J Pharm Biomed Anal. 2013 Feb 23;74:250-6. doi: 10.1016/j.jpba.2012.11.004. Epub 2012 Nov 10.
Montelukast (MKST) is a leukotriene receptor antagonist that has been concomitantly used with inhaled corticosteroids (ICS) for its steroid-sparing effect in the long-term management of asthma. However, the simultaneous determination of MKST, when used as ICS tapering therapy, with ICS in human plasma has not yet been reported. A fast and efficient reversed phase monolith HPLC method was developed for simultaneous determination of MKST with some ICS in plasma of asthmatic patients. The separation was achieved on monolith reversed phase column by isocratic mode at a flow rate of 1.0 ml min(-1) using a mobile phase consisted of a mixture of acetonitrile and 10mM phosphate buffer adjusted to pH 3.5 (40:60, v/v) and detected at 240 nm. Betamethasone dipropionate (BDP) was used as the internal standard. All the studied ICS and MKST were efficiently separated within less than 6 min. The obtained linearity range for the developed HPLC method was 0.03-10 μg ml(-1) with correlation coefficients>0.9995 and the detection limits were 0.009-0.016 μg ml(-1) in plasma for all the studied drugs. The method was validated in agreement with the requirements of US-FDA guideline and was recommended for the target applications. The method is valuable for investigations concerned with the effective tapering of ICS therapy with MKST in patients with chronic asthma in clinical practice without loss of asthma control.
孟鲁司特（MKST）是一种白三烯受体拮抗剂，已与吸入性皮质类固醇（ICS）联合用于哮喘的长期管理，以发挥其皮质类固醇节约作用。然而，MKST 与 ICS 同时用于 ICS 逐渐减量治疗时，在人血浆中的同时测定尚未见报道。本研究建立了一种快速、高效的反相整体柱 HPLC 法，用于同时测定哮喘患者血浆中的 MKST 和一些 ICS。采用等度洗脱模式，以流速 1.0 ml min(-1)，流动相为乙腈和 10mM 磷酸盐缓冲液（pH 3.5）（40:60，v/v），在 monolith 反相柱上进行分离，检测波长为 240nm。倍他米松二丙酸酯（BDP）作为内标。所有研究的 ICS 和 MKST 均能在 6min 内有效分离。所建立的 HPLC 方法的线性范围为 0.03-10 μg ml(-1)，相关系数>0.9995，所有研究药物的检测限均为 0.009-0.016 μg ml(-1)。该方法符合美国 FDA 指南的要求，并推荐用于目标应用。该方法对于在不失去哮喘控制的情况下，在慢性哮喘患者中进行 ICS 治疗与 MKST 有效联合逐渐减量的研究具有重要价值。
