Cruz Lou Ann, Hall Rex
Department of Analytical Chemistry, Alcon Research Limited, 6201 South Freeway, Ft. Worth, TX 76134, USA.
J Pharm Biomed Anal. 2005 Jun 1;38(1):8-13. doi: 10.1016/j.jpba.2004.12.004. Epub 2005 Jan 15.
A capillary electrophoresis method for determining the enantiomeric purity of moxifloxacin hydrochloride in drug substance and ophthalmic/otic drug products was developed and validated. Because moxifloxacin hydrochloride has two chiral centers, the existence of four different isomers is possible. The method was capable of separating moxifloxacin hydrochloride, which is the S,S-isomer, from its potential chiral degradation products, which are the R,R-enantiomer, the R,S-diastereomer, and the S,R-diastereomer. The separation was carried out at 20 degrees C in a 50 microm x 40 cm fused-silica capillary with an applied voltage of -13 kV using a 12.5 mM TEA phosphate buffer (pH 2.5) containing 5% highly-sulfated gamma-cyclodextrin (HS-gamma-CD) and 6% acetonitrile. The detection wavelength was 295 nm. The method was validated with respect to its specificity, linearity, range, accuracy, and precision in the expected range of occurrence for the isomeric impurities (0.05-5%). The method was used to investigate whether racemization was a potential degradation pathway for the drug substance, both in the solid state and in solution.
开发并验证了一种用于测定原料药以及眼科/耳用药品中盐酸莫西沙星对映体纯度的毛细管电泳方法。由于盐酸莫西沙星有两个手性中心，可能存在四种不同的异构体。该方法能够将作为S,S-异构体的盐酸莫西沙星与其潜在的手性降解产物（即R,R-对映体、R,S-非对映体和S,R-非对映体）分离。分离在20℃下于50μm×40cm熔融石英毛细管中进行，施加电压为-13kV，使用含有5%高硫酸化γ-环糊精（HS-γ-CD）和6%乙腈的12.5mM磷酸三乙胺缓冲液（pH2.5）。检测波长为295nm。该方法在异构体杂质预期出现范围（0.05 - 5%）内，就其特异性、线性、范围、准确度和精密度进行了验证。该方法用于研究外消旋化是否是原料药在固态和溶液状态下潜在的降解途径。
