Salem Yomna A, Hammouda Mohammed E A, Abu El-Enin Mohamed A, El-Ashry Saadia M
1Medicinal Chemistry Department, Faculty of Pharmacy, Mansoura University, Mansoura, 35516 Egypt.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Horus University-Egypt (HUE), New Damietta, Egypt.
BMC Chem. 2019 Jun 10;13(1):75. doi: 10.1186/s13065-019-0592-9. eCollection 2019 Dec.
One of the major causes of mortality all over the world is chronic obstructive pulmonary disease (COPD). Recently approved combined inhaler of formoterol fumarate (FF) and glycopyrronium bromide (GLY) has been used in very low concentrations (µg level/actuation) doses in COPD patients. The first spectrophotometric and advanced highly sensitive liquid chromatography has been achieved successfully throughout this study, permitting validated analysis of dual combined inhaler in raw material as well as pharmaceutical inhaled dosage form. Three sensitive analytical methods were carried out for the simultaneous assay of FF and GLY in their novel combined Metered dose inhaler (MDI). The first method depends on measuring the first derivative amplitudes at 208.27 nm for FF and at 213.27 nm and 239.86 nm for GLY, respectively. The second method depends on measurement of the first derivative of the ratio spectra at 214 or 229 nm for FF and 240 or 259 nm for GLY, respectively. For the spectrophotometric methods, the linearity ranges were 0.48-9.6 µg/mL for FF and 0.9-18 µg/mL for GLY. For the third method, valid ion-pairing chromatographic method was carried out applying C column and isocratic mobile phase of 60% v/v acetonitrile and 40% v/v deionized waster (pH 3.0) enclosing 0.025% sodium dodecyl sulfate, using UV detection adjusted to 210 nm and flow rate of 1.2 mL/min. For the ion-pairing chromatographic method, the linearity ranges were 0.048-4.8 µg/mL for FF and 0.09-9.0 µg/mL for GLY. The developed methods are reproducible, valid and offer efficient resolution between formoterol and glycopyrronium using spectrophotometric methods and highly sensitive and precise chromatographic method. The percent recoveries of the inhaled drugs in their MDI were good. The method was successfully established for the quantitative analysis of FF and GLY in their combined pharmaceutical inhaler capsules to validate the therapeutic efficiency of the combined drugs in quality control labs.
慢性阻塞性肺疾病（COPD）是全球主要的致死原因之一。最近获批的富马酸福莫特罗（FF）与格隆溴铵（GLY）联合吸入器已用于COPD患者，剂量极低（每吸微克水平）。在整个研究过程中，首次成功实现了分光光度法和先进的高灵敏度液相色谱法，从而能够对原料药以及药物吸入剂型中的双重联合吸入器进行有效分析。针对新型联合定量吸入器（MDI）中的FF和GLY同时测定，开展了三种灵敏的分析方法。第一种方法是分别测量FF在208.27 nm处以及GLY在213.27 nm和239.86 nm处的一阶导数振幅。第二种方法是分别测量FF在214或229 nm处以及GLY在240或259 nm处的比率光谱的一阶导数。对于分光光度法，FF的线性范围为0.48 - 9.6 μg/mL，GLY的线性范围为0.9 - 18 μg/mL。对于第三种方法，采用C柱和60% v/v乙腈与40% v/v去离子水（pH 3.0）的等度流动相，其中含有0.025%的十二烷基硫酸钠，进行有效的离子对色谱法，使用紫外检测，检测波长调至210 nm，流速为1.2 mL/min。对于离子对色谱法，FF的线性范围为0.048 - 4.8 μg/mL，GLY的线性范围为0.09 - 9.0 μg/mL。所开发的方法具有重现性、有效性，并且使用分光光度法以及高灵敏度和精确的色谱法能够在福莫特罗和格隆溴铵之间实现有效分离。吸入药物在其MDI中的回收率良好。该方法成功用于联合药物吸入胶囊中FF和GLY的定量分析，以在质量控制实验室中验证联合药物的治疗效果。
