酮洛芬对映体的分离、分析方法研究及其应用
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摘要
本文考察酮洛芬对映体在多糖类手性色谱柱( Chiralpak AD柱、Chiralcel OJ柱、Chiralpak AS柱和Chiralcel OD柱)上的色谱行为以及流动相组成对对映体分离的影响,建立酮洛芬对映体的分离分析方法,并用于血浆样品中酮洛芬对映异构体的测定。以Chiralpak AD(10μm,250mm×4.6mm i.d. Daicel Chemicals)为色谱柱,正己烷-异丙醇-TFA(80:20:0.02,v/v/v)为流动相,检测波长254 nm,流速1.0 ml/min,柱温25℃作为色谱条件分离分析血浆样品中的酮洛芬对映异构体,结果酮洛芬对映体在10 min内实现分离,分离度大于2.0,对映体R和S分别在血药浓度0.1μg/ml - 10μg/ml范围内线性关系良好相关因子分别为0.9998和0.9996,单一对映体的最低检测限均为2 ng (S/N=3)。该方法操作简单、灵敏度高、准确度好,可用于单一对映异构体的光学纯度检测及药代动力学研究。
The separation effect for the enantiomers of ketoprofen on four diferent polysaccharide-derivative chiral stationary phases was investigated and a stereospecific HPLC method was developed for the determination of ketoprofen enantiomers in animal plasma. The enantiomers of ketoprofen were resolved in the normal phase mode by using N-hexane- isopropanol-TFA( 80:20:0.02,v/v/v)as mobile phase at the flow rate of 1.0ml/min with the UV detector at a wavelength of 254 nm. The resolution is more than 2.0, the detection limit (S/N=3 ) was 2 ng for each enantiomer. Linear calibration curves were obtained in the range 0.1–10μg/ml for R-(+)-ketoprofen (r=0.9998) and S-(+ )-ketoprofen (r=0.9996) in plasma.This method is simple, fast and can be used to detect optical purity of S-(+)-ketoprofen and monitor pharmacokinetic studies of ketoprofen enantiomers.
The separation effect for the enantiomers of ketoprofen on four diferent polysaccharide-derivative chiral stationary phases was investigated and a stereospecific HPLC method was developed for the determination of ketoprofen enantiomers in animal plasma. The enantiomers of ketoprofen were resolved in the normal phase mode by using N-hexane- isopropanol-TFA( 80:20:0.02,v/v/v)as mobile phase at the flow rate of 1.0ml/min with the UV detector at a wavelength of 254 nm. The resolution is more than 2.0, the detection limit (S/N=3 ) was 2 ng for each enantiomer. Linear calibration curves were obtained in the range 0.1–10μg/ml for R-(+)-ketoprofen (r=0.9998) and S-(+ )-ketoprofen (r=0.9996) in plasma.This method is simple, fast and can be used to detect optical purity of S-(+)-ketoprofen and monitor pharmacokinetic studies of ketoprofen enantiomers.
引文
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