A novel high-throughput sample pretreatment system was developed by the integration of protein precipitation (PP), phospholipid removal (PPR), and hollow fiber liquid-phase microextraction (HF-LPME) into two simple 96-well plates and a matching 96-grid lid. With this system, 16 steroids were separated from biological matrices of plasma, milk, and urine and analyzed by liquid chromatography–triple quadrupole mass spectrometry. In the tandem sample cleanup process, the prepositive PP and PPR step preliminarily removed some of the interferences from the biological matrices. The following HF-LPME step kept the residual interference out of the hollow fiber and enriched the steroids in the hollow fiber to achieve high sensitivity. By a series of method optimizations, acetonitrile was chosen as the crash solvent for PP and PPR. A mixture of octanol and toluene (1:1 v/v) was used as the acceptor phase for HF-LPME. The extraction was conducted at 80 rpm for 50 min in a donor phase containing 1 mL 20 % sodium chloride at 25 °C. Under these conditions, the limits of detection for the 16 steroids were 3.6–300.0 pg.mL-1 in plasma, 3.0–270.0 pg.mL-1 in milk, and 2.2–210.0 pg.mL-1 in urine. The recoveries of the 16 steroids were 81.9–97.9 % in plasma (relative standard deviation 1.0–8.0 %), 80.6–97.7 % in milk (relative standard deviation 0.8–5.4 %), and 87.3–98.7 % in urine (relative standard deviation 1.0–4.9 %). Further, the integrated 96-well platform of PP, PPR, and HF-LPME enabled us to run this assay in an automatic and high-throughput fashion. The reliability of the method was further corroborated by evaluation of its applicability in plasma and urine samples from volunteers and fresh bovine milk from local dairy enterprises.

A novel carbosilane dendrimer bonded silica (G2-silica) was synthesized and evaluated as a potential chromatographic resin. The G2-silica was characterized by using various analytical techniques, such as infrared spectroscopy, elemental analysis and loss on ignition analysis. The G2-silica was packed into a capillary and used as the stationary phase for capillary electrochromatography (CEC). The packing characteristics such as the electric current vs. the applied voltage, the effects of voltage, pH, and acetonitrile concentration on EOF, the hydrophobic selectivity, and the repeatability were all investigated. Seven model compounds including thiourea, benzene, ethyl benzene, butyl benzene, benzyl alcohol, toluene and naphthalene were well separated on the CEC column with the separation efficiencies ranging from 40000 to 90000 plates per meter. The repeatability was satisfactory with the RSD of the migration time (2.4%). These results indicate that carbosilane dendrimer bonded silica can be used as a novel packing material which has the characteristics of a typical reversed phase.

•A novel 96-throughput screening system was designed.•The log D values of 13 drugs were successfully and accurately measured.•It is an accurate, precise, and reliable 96-throughput log D measuring method.•It would be a tool in drug screening, environment analysis, and other fields.This paper describes the development of a novel high-throughput hollow fiber membrane solvent microextraction technique for the simultaneous measurement of the octanol/water distribution coefficient (log D) for organic compounds such as drugs. The method is based on a designed system, which consists of a 96-well plate modified with 96 hollow fiber membrane tubes and a matching lid with 96 center holes and 96 side holes distributing in 96 grids. Each center hole was glued with a sealed on one end hollow fiber membrane tube, which is used to separate the aqueous phase from the octanol phase. A needle, such as microsyringe or automatic sampler, can be directly inserted into the membrane tube to deposit octanol as the accepted phase or take out the mixture of the octanol and the drug. Each side hole is filled with aqueous phase and could freely take in/out solvent as the donor phase from the outside of the hollow fiber membranes. The log D can be calculated by measuring the drug concentration in each phase after extraction equilibrium. After a comprehensive comparison, the polytetrafluoroethylene hollow fiber with the thickness of 210 μm, an extraction time of 300 min, a temperature of 25 °C and atmospheric pressure without stirring are selected for the high throughput measurement. The correlation coefficient of the linear fit of the log D values of five drugs determined by our system to reference values is 0.9954, showed a nice accurate. The −8.9% intra-day and −4.4% inter-day precision of log D for metronidazole indicates a good precision. In addition, the log D values of eight drugs were simultaneously and successfully measured, which indicated that the 96 throughput measure method of log D value was accurate, precise, reliable and useful for high throughput screening.

A novel carbosilane dendrimer bonded silica (G2-silica) was synthesized and evaluated as a potential chromatographic resin. The G2-silica was characterized by using various analytical techniques, such as infrared spectroscopy, elemental analysis and loss on ignition analysis. The G2-silica was packed into a capillary and used as the stationary phase for capillary electrochromatography (CEC). The packing characteristics such as the electric current vs. the applied voltage, the effects of voltage, pH, and acetonitrile concentration on EOF, the hydrophobic selectivity, and the repeatability were all investigated. Seven model compounds including thiourea, benzene, ethyl benzene, butyl benzene, benzyl alcohol, toluene and naphthalene were well separated on the CEC column with the separation efficiencies ranging from 40000 to 90000 plates per meter. The repeatability was satisfactory with the RSD of the migration time (2.4%). These results indicate that carbosilane dendrimer bonded silica can be used as a novel packing material which has the characteristics of a typical reversed phase.