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The capability of biopartitioning micellar chromatography (BMC), using pure Brij35 solution and mixed micellar system of Brij35-SDS (85:15) as mobile phase, to describe and estimate bioactivities of angiotensin converting enzyme inhibitors at different pH has been studied. Quantitative retention-activity relationships (QRAR) in BMC were investigated for these compounds. The obtained BMC(Brij35-SDS)-QRAR models were compared with the traditional BMC(Brij35)-QRAR, and better statistically models were obtained using Brij35-SDS retention data. The superiority of BMC(Brij35-SDS)-QRAR is due to the fact that the mixed micellar mobile phase can simulate the resting membrane potential and the conformation of the long hydrophilic polyoxyethylene chains remains unchanged.

Biopartitioning micellar chromatography (BMC) is a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 under adequate experimental conditions and can simulate biopartioning process of many kinds of drugs and describe their biological behavior. The capability of BMC to describe and estimate pharmacokinetic and pharmacodynamic parameters of angiotensin-converting enzyme inhibitors (ACEIs) had been studied in this paper. The correlation between retention factors of ACEIs obtained using BMC and bioactivity parameters (half-life, volume of distribution, clearance, and IC(50)) was investigated utilizing a second-order polynomial model. The P-values obtained for half-life, volume of distribution, clearance, and IC(50) models were less than 0.05, and the r(2) of those four models were 0.89, 0.98, 0.94, and 0.97, with r(2)(adj) (adjusted for freedom degrees) being 0.85, 0.98, 0.91, and 0.95, respectively. The predictive and interpretative ability of the chromatographic models was evaluated in terms of cross-validated data [root mean squared error of calibration (RMSEC), root mean squared error of cross-validation (leave-one-out) (RMSECV), and root mean squared error of cross-validation (leave-one-out) for interpolated data (RMSECVi)]. The quantitative retention-activity relationship (QRAR) models of ACEIs developed in this paper may be a useful approach to screening new chemicals in the early stage of development.

Triptolide (TP) is one of the most important biologically active components of the Chinese herb Tripterygium wilfordii Hook f (TWHf). A novel high-performance liquid chromatography/mass spectrometry (LC/MS) method was developed to study the kinetic release of TP after intravenous injection of the newly synthesized 14-succinyl triptolide-lysozyme (TPS-LZM). The method was validated in terms of selectivity, linearity, precision, accuracy, stability, limit of detection (LOD) and limit of quantification (LOQ). The calibration curve was linear over the concentration range 0.5-400.0 ng/g. The mean recovery of triptolide from spiked samples, in a concentration range of 0.5-400.0 ng/g, was 91.84% (RSD = 3.69%, n = 3). The intra- and inter-assay coefficients of variation were less than 6.38%. The method with simple sample pretreatment and being highly specific and precise, can be used for analysis of triptolide release in rat kidney after intravenous injection of renal-targeting TPS-LZM conjugate. The results showed that, as compared with free TP, TPS-LZM could significantly increase the concentration and prolong the action time of TP in the kidney.

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