手性NACE法测定富马酸福莫特罗粉吸入剂中富马酸福莫特罗对映体的含量

Determination of the enantiomers of formoterol fumarate in formoterol fumarate powder inhaler by chiral NACE

关键词:  非水毛细管电泳法  手性分离  富马酸福莫特罗粉吸入剂  L(+)-酒石酸–硼酸络合酸

Key words:  nonaqueous capillary electrophoresis  chiral separation  formoterol fumarate powder inhaler  L(+)-tartaric acid–boric acid complex

摘要:

目的 以L(+)-酒石酸–硼酸络合酸为手性选择剂，建立手性非水毛细管电泳法，对富马酸福莫特罗进行手性分离，并测定富马酸福莫特罗粉吸入剂中对映体的含量。方法 以未涂层熔融弹性石英毛细管（65.0 cm × 50 μm，有效长度45.0 cm）为分离通道；运行电压20 kV；检测波长214 nm；室温；优化的背景缓冲液为含40 mmol·L-1 L(+)-酒石酸、400 mmol·L-1硼酸、0.4%（v/v）三乙胺的甲醇溶液。结果 富马酸福莫特罗的两个对映体在优化的手性分离条件下能够被完全分离，分离度为9.5；出峰顺序为RR-FMT在前，SS-FMT在后；在2.5 ~ 250.0 μg·mL-1范围内，两个对映体的质量浓度与峰面积分别呈现良好的线性关系；RR-FMT和SS-FMT的加标回收率在99.2% ~ 101.8%之间，相对标准偏差为1.2% ~ 1.9%，表明该法准确度良好；RR-FMT和SS-FMT的标示量百分含量分别为98.5%和99.1%，相对标准偏差分别为1.3%和1.5%。结论 此方法可用于富马酸福莫特罗粉吸入剂中对映体的含量测定。

Abstract:

OBJECTIVE To establish a chiral nonaqueous capillary electrophoresis (NACE) method, L(+)-tartaric acid–boric acid complex was used as the chiral selector for the chiral separation and determination of the enantiomers of formoterol fumarate in formoterol fumarate powder inhaler. METHODS An uncoated fused silica capillary (65.0 cm × 50 μm, and an effective length of 45.0 cm) was used as the separation channel, along with the applied voltage of 20 kV, detection wavelength of 214 nm, room temperature. The optimized background buffer was the methanol solution containing 40 mmol·L-1 L(+)-tartaric acid, 400 mmol·L-1 boric acid, and 0.4%(v/v) triethylamine. RESULTS The two enantiomers of formoterol fumarate could be completely separated under the optimized chiral separation conditions, and the Rs was 9.5. The migration order was the former RR-FMT and the later SS-FMT. Good linearity of the peak area for the two enantiomers were showed in the concentration range of 2.5 ~ 250.0 μg·mL-1, respectively. The recoveries of RR-FMT and SS-FMT were 99.2% ~ 101.8%, with relative standard deviations (RSDs) of 1.2% ~ 1.9%, indicating good accuracy of the method. The percentage of labeled quantities were 98.5% and 99.1% for RR-FMT and SS-FMT, with RSDs of 1.3% and 1.5%, respectively. CONCLUSION The method was suitable for the determination of the enantiomer contents in formoterol fumarate powder inhaler.