Simó C, Gallardo A, San Román J, Barbas C, Cifuentes A
Inst de Fermentaciones Industriales (CSIC), Madrid, Spain.
J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Feb 5;767(1):35-43. doi: 10.1016/s0378-4347(01)00533-3.
In this work, the capability of two polymeric drug delivery systems (DDS) containing racemic ibuprofen (IBU) for controlled release of IBU in different media was studied carrying out assays in-vitro. To quantitatively monitor the release of R(-)- and S(+)-IBU, a fast, sensitive and inexpensive capillary electrophoresis (CE) method was developed. To do this, different chiral selectors, temperatures, buffer compositions and pHs were tested. This new CE method uses bare silica columns together with a buffer containing 6% Dextrin in a 150 mM sodium tetraborate buffer at pH 9. Baseline separations of R(-)- and S(+)-IBU were achieved in less than 5 min at 20 degrees C. By using this method, both enantiomers can be determined at concentrations as low as 1 microg/ml, allowing the detection of enantiomeric percentages of 0.5% of R(-)-IBU in the presence of 99.5% of the optical antipode. Moreover, the method shows a high reproducibility for the same day and different days. The usefulness of this method to quantitatively monitor the release of R(-)- and S(+)-IBU from two different polymeric DDS is demonstrated. It is shown that the release rate of IBU depends on the spacer of the side residue used in the polymeric device. Also, it is demonstrated that the release of both enantiomers is enzymatically activated in rat plasma.
在本研究中,通过体外试验研究了两种含有外消旋布洛芬(IBU)的聚合物药物递送系统(DDS)在不同介质中控制IBU释放的能力。为了定量监测R(-)-和S(+)-IBU的释放,开发了一种快速、灵敏且廉价的毛细管电泳(CE)方法。为此,测试了不同的手性选择剂、温度、缓冲液组成和pH值。这种新的CE方法使用未涂渍的硅胶柱,结合在pH 9的150 mM硼酸钠缓冲液中含有6%糊精的缓冲液。在20℃下,不到5分钟即可实现R(-)-和S(+)-IBU的基线分离。使用该方法,两种对映体均可在低至1μg/ml的浓度下测定,在存在99.5%光学对映体的情况下,可检测到0.5%的R(-)-IBU对映体百分比。此外,该方法在同一天和不同天均显示出高重现性。证明了该方法在定量监测两种不同聚合物DDS中R(-)-和S(+)-IBU释放方面的实用性。结果表明,IBU的释放速率取决于聚合物装置中使用的侧链残基的间隔基。此外,还证明了两种对映体在大鼠血浆中均可被酶激活释放。