Andersen Solveig, Halvorsen Trine Grønhaug, Pedersen-Bjergaard Stig, Rasmussen Knut E, Tanum Lars, Refsum Helge
School of Pharmacy, University of Oslo, P.O. Box 1068 Blindern, 0316 Oslo, Norway.
J Pharm Biomed Anal. 2003 Sep 19;33(2):263-73. doi: 10.1016/s0731-7085(03)00264-4.
A chiral capillary electrophoresis (CE) system allowing simultaneous enantiomer determination of citalopram (CIT) and its pharmacologically active metabolite desmethylcitalopram (DCIT) was developed. Excellent chiral separation was obtained using 1% sulfated-beta-cyclodextrin (S-beta-CD) as chiral selector in combination with 12% ACN in 25 mM phosphate pH 2.5. Samples were prepared by liquid-phase microextraction (LPME) based on a rodlike porous polypropylene hollow fibre. CIT and DCIT were extracted from 1 ml plasma made alkaline with NaOH, into dodecyl acetate impregnated in the pores of a hollow fibre, and into 20 mM phosphate pH 2.75, inside the hollow fibre. The acceptor solution was directly compatible with the CE system. Efficient sample clean-up was seen, and the recoveries were 46 and 29% for the enantiomers of CIT and DCIT, respectively, corresponding to 31 and 19 times enrichment. The limit of quantification (S/N=10) was <11.2 ng/ml, intra-day precision was <12.8% RSD, and inter-day precision was <14.5% RSD, for all enantiomers. The validated method was successfully applied to simultaneous determination of enantiomer concentrations of CIT and DCIT in plasma samples from nine patients treated with racemic citalopram. The results confirm LPME-CE as a suitable and promising tool for enantiomeric determination of chiral drugs and metabolites in biological matrices.
开发了一种手性毛细管电泳（CE）系统，可同时测定西酞普兰（CIT）及其药理活性代谢物去甲基西酞普兰（DCIT）的对映体。使用1%硫酸化β-环糊精（S-β-CD）作为手性选择剂，在25 mM磷酸盐pH 2.5的缓冲液中加入12%乙腈（ACN），实现了优异的手性分离。样品通过基于棒状多孔聚丙烯中空纤维的液相微萃取（LPME）进行制备。将1 ml用NaOH碱化的血浆中的CIT和DCIT萃取到浸渍在中空纤维孔中的乙酸十二酯中，再萃取到中空纤维内部20 mM磷酸盐pH 2.75的溶液中。接受相溶液可直接与CE系统兼容。实现了高效的样品净化，CIT和DCIT对映体的回收率分别为46%和29%，相当于富集了31倍和19倍。所有对映体的定量限（S/N = 10）<11.2 ng/ml，日内精密度<12.8% RSD，日间精密度<14.5% RSD。该经过验证的方法成功应用于同时测定9例接受消旋西酞普兰治疗患者血浆样品中CIT和DCIT对映体的浓度。结果证实LPME-CE是用于生物基质中手性药物和代谢物对映体测定的合适且有前景的工具。
