Guorong Fan

Paclitaxel (PTX) is one of the most widely used chemotherapeutic agents. The commercial PTX formulation was based on Cremophor EL and ethanol owing to its poor aqueous solubility. However, Cremophor EL has been shown to cause toxic effects such as life‐threatening anaphylaxis. In our study, we diluted PTX in a commercially available 20% (w/v) lipid emulsion (Lip‐PTX) in order to avoid Cremophor EL. The purpose of this study was to evaluate the pharmacokinetics and tissue distributions between Lip‐PTX and PTX injection. We also investigated the effects of Lip‐PTX and PTX injection on human gastric cancer cells HGC‐27 by MTT assay. The apoptosis was detected by flow cytometry with Annexin V/propidium iodide (PI) double staining. Furthermore, the safety such as acute toxicity was also assessed. The results showed that PTX in Sprague–Dawley rats administered Lip‐PTX exhibited extended half‐life, increased clearance (P < 0.05) and smaller area under the concentration–time curve compared with PTX injection and there was little significant difference in the distribution of PTX in Sprague–Dawley rats or tumor‐bearing mice between Lip‐PTX and PTX injection. The cells treated with Lip‐PTX had a higher percentage of apoptosis and a higher G₂/M phase ratio, which indicated that the anticancer effect of Lip‐PTX was significantly better than that of PTX injection. Moreover, our study highlighted the safety of Lip‐PTX. This study demonstrated the feasibility and potential advantages of Lip‐PTX for clinical therapy.

A fast and high‐sensitivity liquid chromatography–tandem mass spectrometry (LC–MS/MS) method assisted by microdialysis was established for the determination of meropenem in total parenteral nutrition (TPN) infused plasma. A 10‐times dilution was arranged for sample preparation to overcome the severe matrix effect caused by the high salt content in dialysate and complex composition of TPN. This quantification method was proved to be satisfied in selectivity, accuracy, precision, linearity (R² > 0.998), recovery, matrix effect and stability. In the optimized conditions, the calibration curve range was set from 2 to 2000 ng/ml. This validated method was applied to pharmacokinetics study of meropenem in rabbits with sepsis (induced by cecal ligation and punctures) under simultaneous infusion of TPN to simulate the clinical practice. The results demonstrated that the LC–MS/MS method assisted by microdialysis can be used successfully for the determination of meropenem in TPN‐infused plasma. Moreover, the area under the curve and the maximum concentrations in the plasma of meropenem in control rabbits were significantly smaller (P < 0.05), while clearance and distribution volumes were significantly greater (P < 0.05) than in those with sepsis. It could be speculated that drug monitoring in patients with sepsis may be necessary.

Sodium Danshensu (sodium d-(+)-β-(3,4-dihydroxyphenyl) lactate), one of the water-soluble ingredients in Salvia miltiorrhiza, exhibits potent relaxation of the coronary artery and anticoagulation effection. A high-throughput, rapid, and sensitive method combining liquid chromatography with electrospray ionization tandem mass spectrometry to determine the sodium danshensu in beagle dog plasma was developed and validated, using gallic acid as an internal standard (IS). Acidified plasma samples were extracted using 96-well liquid-liquid extraction, and were eluted on a CNW Athena C18 column (3 μm, 2.1 × 100 mm) by using a gradient mobile phase system of methanol and water (containing 0.2% formic acid). The mass spectrometric detection was achieved using negative ion electrospray ionization mode and monitoring the precursor→production combinations of m/z 197→135 for sodium danshensu and 169→125 for IS, in multiple reaction monitoring modes. Good linearity was achieved, and the linear range was 10–1000 ng/mL (R² > 0.996) with a quantification limit of 10 ng/mL for sodium danshensu in beagle dog plasma. The intra- and inter-day precision (RSD) ranged from 2.1% to 9.0%. The accuracy (RE) was between −8.6% and 5.7% at all quality control levels. The validated method was successfully applied to the pharmacokinetics study of sodium danshensu in beagle dog plasma after intravenous injection and oral administration of sodium danshensu.

A method using liquid chromatography-electrospray ionization ion trap mass spectrometry was established for the identification of metabolites in feces, urine and bile in rats after oral administration of 3′,4′-dimethoxy flavonol-3-β-d-glucopyranoside (abbreviated DF3G). Seven metabolites in rat feces, urine and bile were firstly identified on the basis of their MS fragmentation behaviors. Three metabolites were identified in the feces, 6 in the urine and 2 in the bile, which suggested that demethylation, deglycosylation and deglycosylation followed by glucuronide conjugation were the major metabolic pathways for DF3G in vivo. Hydrolyzation might be the first step in the absorption and metabolism of DF3G. The possible metabolic pathway was proposed for the first time. The established method was simple, reliable and sensitive, revealing that it could be used to rapidly screen and identify the structures of metabolites of DF3G to better understand its metabolism in vivo.