PMID- 34812008 OWN - NLM STAT- MEDLINE DCOM- 20211124 LR - 20220915 IS - 1872-2059 (Electronic) IS - 1000-8713 (Print) IS - 1000-8713 (Linking) VI - 39 IP - 12 DP - 2021 Dec TI - [Determination of the enantiomers of salmeterol xinafoate in salmeterol fluticasone powder inhalant by chiral nonaqueous capillary electrophoresis]. PG - 1355-1361 LID - 10.3724/SP.J.1123.2021.06002 [doi] AB - Salmeterol xinafoate (SalX) is one of the ideal drugs used for the treatment of nocturnal asthma attacks and daily maintenance. The molecular structure of SalX contains a chiral carbon atom, and thus, SalX has two enantiomers, viz. (R)-SalX and (S)-SalX. It is clinically administered in the racemic form. Related studies have shown that the two enantiomers of SalX are quite different in pharmacology, toxicology, and other aspects. Therefore, it is of great significance to establish an analytical method for the chiral separation and determination of the SalX enantiomers to guarantee their quality and ensure their safety and effectiveness in clinical use. In this study, a chiral nonaqueous capillary electrophoresis (NACE) method, using a L(+)-tartaric acid-boric acid complex as the chiral selector, was established to determine the enantiomers of SalX in salmeterol fluticasone powder inhalant. The L(+)-tartaric acid-boric acid complex was synthesized in situ by the reaction of L(+)-tartaric acid and boric acid in methanol solution. The ion pair principle was considered the enantioseparation mechanism, and the non-aqueous system was found to be more favorable for ion pair formation, which is useful for chiral recognition. Chiral separation is based on the reversible formation of diastereomeric ion pairs between the negatively charged L(+)-tartaric acid-boric acid complex and the positively charged salmeterol enantiomers. Due to the difference in ion-pair binding ability between different enantiomers, the apparent electrophoretic mobilities of different enantiomers were also different, resulting in chiral separation in NACE. To achieve good resolution, the effects of L(+)-tartaric acid concentration, boric acid concentration, and apparent pH (pH(*) ) on the chiral separation were investigated. The optimized buffer solution (pH(*) 0.93) contained 120.0 mmol/L L(+)-tartaric acid and 120.0 mmol/L boric acid in methanol. Other experimental conditions were as follows: uncoated fused-silica capillary with an I. D. of 50.0 mum, a total length (L(tot)) of 64.5 cm, and an effective length (L(eff)) of 55.5 cm, along with gravity injection of 17.5 cmx10.0 s, detection wavelength of 225 nm, room temperature, and operating voltage of 20.0 kV. Under these experimental conditions, the two enantiomers of SalX achieved a resolution of 2.18 within 18.0 min. Both enantiomers showed a good linear relationship of the peak area in the concentration range of 27.5-800.0 mg/L, the correlation coefficient (r) being greater than 0.9990. The detection limit (S/N=3) and quantitative limit (S/N=10) were 7.5 mg/L and 25.0 mg/L, respectively; the standard recovery was 98.1%-101.9%, with relative standard deviations (RSDs) of 1.2%-1.9%. The intra- and inter-day precisions were examined, and the RSDs of the peak area and migration time were found to be below 4.9% and 1.9%, respectively, indicating good repeatability (inter-day) and reproducibility (inter-day) of the method. The established chiral NACE method was used to determine the two SalX enantiomers in a random salmeterol fluticasone powder inhalant purchased from a local market. The results showed that the percentage of labeled quantities was 98.7% for both enantiomer 1 and enantiomer 2, with RSDs of 2.5% and 2.7%, respectively. Thus, this method is simple, feasible, accurate, and inexpensive, and can be applied for the determination of SalX enantiomers in commercially available salmeterol fluticasone powder inhalants. FAU - Zhang, Xu AU - Zhang X AD - Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Institute of Life Science and Green Development, College of Pharmaceutical Sciences, Hebei University, Baoding 071002, China. FAU - Dong, Miaoxue AU - Dong M AD - Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Institute of Life Science and Green Development, College of Pharmaceutical Sciences, Hebei University, Baoding 071002, China. FAU - Xu, Yin AU - Xu Y AD - Tianjin Alta Scientific Co., Ltd., Tianjin 300457, China. FAU - Wang, Lijuan AU - Wang L AD - Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Institute of Life Science and Green Development, College of Pharmaceutical Sciences, Hebei University, Baoding 071002, China. FAU - Qiao, Xiaoqiang AU - Qiao X AD - Key Laboratory of Pharmaceutical Quality Control of Hebei Province, Institute of Life Science and Green Development, College of Pharmaceutical Sciences, Hebei University, Baoding 071002, China. LA - chi PT - Journal Article PL - China TA - Se Pu JT - Se pu = Chinese journal of chromatography JID - 9424804 RN - 0 (Powders) RN - 6EW8Q962A5 (Salmeterol Xinafoate) RN - CUT2W21N7U (Fluticasone) SB - IM MH - *Electrophoresis, Capillary MH - Fluticasone MH - Powders MH - Reproducibility of Results MH - Salmeterol Xinafoate MH - Stereoisomerism PMC - PMC9404210 OTO - NOTNLM OT - L(+)-tartaric acid-boric acid complex OT - enantiomer OT - nonaqueous capillary electrophoresis (NACE) OT - salmeterol fluticasone powder inhalant EDAT- 2021/11/24 06:00 MHDA- 2021/11/25 06:00 PMCR- 2021/12/08 CRDT- 2021/11/23 07:00 PHST- 2021/11/23 07:00 [entrez] PHST- 2021/11/24 06:00 [pubmed] PHST- 2021/11/25 06:00 [medline] PHST- 2021/12/08 00:00 [pmc-release] AID - 1000-8713-39-12-1355 [pii] AID - 10.3724/SP.J.1123.2021.06002 [doi] PST - ppublish SO - Se Pu. 2021 Dec;39(12):1355-1361. doi: 10.3724/SP.J.1123.2021.06002.