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This project evaluated solid-phase extraction (SPE) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to determine the trace amount of rosiglitazone in human urine. The analytical performance of four modes of LC-MS and tandem MS operation (atmospheric pressure chemical ionization (APCI), electrospray ionization (ESI), positive and negative ionization) was compared for two mass spectrometers, a triple-quadrupole and a quadrupole ion trap instrument. Rosiglitazone was extracted from urine using a SPE cartridge of 50mg C8 sorbent and acetonitrile used as the eluting solvent. Samples were then separated on a RP18 column interfaced with a tandem mass spectrometer. The recovery of rosiglitazone was greater than 91.2%. The urine assay combining SPE and LC-APCI-MS/MS of triple-quadrupole was proved a very selective and sensitive method for determination of trace rosiglitazone. The assay was linear over a wide range, with a lower limit of quantification of 0.1 ng/mL using 1 mL of urine. The intra- and inter-day precisions were9.8% and7.9%, respectively, and the accuracies were in the range 91.0-103.6%. The rosiglitazone concentration profile in human urine was also determined. The results of this study reveal the adequacy of SPE-LC-APCI-MS/MS method for analyzing rosiglitazone from diabetic patients' urines. The concentrations of rosiglitazone were detected to range from 760 to 164 pg/mL.

The aim of this study was to evaluate dynamic changes in energy-related metabolites in the cortex of gerbils subjected to focal cerebral ischemia after pretreatment with Ginkgo biloba extract. Focal cerebral ischemia was induced by occlusion of the right common carotid artery and the right middle cerebral artery for 60 min in anesthetized gerbils. A microdialysis probe was inserted into the cortex to monitor extracellular lactate. pyruvate and ascorbate during ischemia and reperfusion. The present study demonstrated a dynamic decrease in pyruvate (25% of baseline) and increases in lactate (160% of baseline) and asorbate (300% of baseline) and a 5-fold increase in the lactate:pyruvate (L:P) ratio during cerebral ischemia in the control group. However. pyruvate levels were preserved and ascorbate levels were enhanced with a chronic pretreatment of Ginkgo biloba extract for 8 days (i.p., 100 mg kg(-1) day(-1)). Preservation of pyruvate and enhancement of ascorbate observed in this study may be associated with the neuroprotective effects of Ginkgo biloba extract.

The disposition and biliary excretion of omeprazole was investigated following i.v. administration to rats at 10 mg/kg. We used a microdialysis technique coupled to a validated microbore HPLC system to monitor the levels of protein-unbound omeprazole in rat blood, brain and bile, constructing the relationship of the time course of the presence of omeprazole. Microdialysis probes were simultaneously inserted into the jugular vein toward right atrium, the brain striatum and the bile duct of the male Sprague-Dawley rats for biological fluid sampling after the administration of omeprazole (10 mg/kg) through the femoral vein. The concentration-response relationship from the present method indicated linearity (r2>0.995) over a concentration range of 0.01-50 microg/ml for omeprazole. Intra-assay and inter-assay precision and accuracy of omeprazole fell well within the predefined limits of acceptability. Following omeprazole administration, the blood-to-brain coefficient of distribution was 0.15, which was calculated as the area under the concentration versus time curve (AUC) in the brain divided by the AUC in blood (k=AUCbrain/AUCblood). The blood-to-bile coefficient of distribution (k=AUCbile/AUCblood) was 0.58. The decline of unbound omeprazole in the brain striatum, blood and bile fluid suggests that there was rapid exchange and equilibration between the compartments of the peripheral and central nervous systems. In addition, the results indicated that omeprazole was able to penetrate the blood-brain barrier and undergo hepatobiliary excretion.

A microdialysis method followed by a microbore liquid chromatographic ultraviolet detection procedure has been performed for the assay of unbound cefsulodin in rat blood. A microdialysis probe was inserted into the jugular vein for blood sampling. This method involves an on-line design for submitting dialysate into the liquid chromatographic system. The chromatographic conditions consisted of a mobile phase of methanol-100 mM monosodium phosphoric acid (10:90, v/v, pH 5.0) pumped through a microbore reversed-phase column at a flow-rate of 0.05 ml/min. Detection wavelength was set at 265 nm. Microdialysis probes, being laboratory-made, were screened for acceptable in vivo recovery while chromatographic resolution and detection were validated for response linearity as well as intra- and inter-day variabilities. The method was then applied to pharmacokinetics profiling of cefsulodin in the blood following intravenous administration of cefsulodin (20 mg/kg) in rats. Pharmacokinetics were calculated from the corrected data for dialysate concentrations of cefsulodin versus time. Based on pharmacokinetic calculation, cefsulodin best fitted to a two-exponential disposition. This study provided specific pharmacokinetic information for protein-unbound cefsulodin and demonstrated the applicability of this continuous sampling method for pharmacokinetic study.

Microwave-assisted extraction (MAE), was used to extract sunscreen agents from cosmetic products. The extracts were analyzed by liquid chromatography (LC). The present method allows the determination of three sunscreen agents, Eusolex 2292, 4360 and 6300. The precision of the assay at 40 microg/ml of sunscreen agents ranged from 1.5 to 2.2%, and the detection limits were 2.0-4.0 ng/ml.