A novel dispersive liquid‐liquid microextraction that combines self‐induced acid‐base effervescent reaction and manual shaking, coupled with ultra high performance liquid chromatography with tandem mass spectrometry was developed for simultaneous determination of ten neonicotinoid insecticides and metabolites in orange juice. An innovative aspect of this method was the utilization of the acidity of the juice for a self‐reaction between acidic components contained in the juice sample and added sodium carbonate which generated carbon dioxide bubbles in situ, accelerating the analytes transfer to the extractant of 1‐undecanol. The total acid content of juice sample was measured to produce the maximum amount of bubbles with minimum usage of carbonate. Manual shaking was subsequently adopted and was proven to enhance the extraction efficiency. The factors affecting the performance, including the type and the amount of the carbon dioxide source and extractant, and ionic strength were optimized. Compared with conventional methods, this approach exhibited low limits of detection (0.001–0.1 µg/L), good recoveries (86.2–103.6%), high enrichment factors (25–50), and negligible matrix effects (−12.3–13.7%). The proposed method was demonstrated to provide a rapid, practical, and environmentally friendly procedure due to no acid reagent, toxic solvent, or external energy requirement, giving rise to potential application on other high acid‐content matrices.

Xanthine oxidase (XOD) inhibition has long been considered an effective anti-hyperuricemia strategy. To identify effective natural XOD inhibitors with little side effects, we performed a XOD inhibitory assay-coupled isolation of compounds from Smilacis Glabrae Rhizoma (SGR), a traditional Chinese medicine frequently prescribed as anti-hyperuricemia agent for centuries. Through the in vitro XOD inhibitory assay, we obtained a novel XOD inhibitor, 5-O-caffeoylshikimic acid (#1, 5OCSA) with IC50 of 13.96 μM, as well as two known XOD inhibitors, quercetin (#3) and astilbin (#6). Meanwhile, we performed in silico molecular docking and found 5OCSA could interact with the active sites of XOD (PDB ID: 3NVY) with a binding energy of −8.6 kcal/mol, suggesting 5OCSA inhibits XOD by binding with its active site. To evaluate the in vivo effects on XOD, we generated a hyperuricemia mice model by intraperitoneal injection of potassium oxonate (300 mg/kg) and oral gavage of hypoxanthine (500 mg/kg) for 7 days. 5OCSA could inhibit both hepatic and serum XOD in vivo, together with an improvement of histological and multiple serological parameters in kidney injury and HUA. Collectively, our results suggested that 5OCSA may be developed into a safe and effective XOD inhibitor based on in vitro, in silico and in vivo evidence.

H3B‐6545 is a selective ERα covalent antagonist, which has been demonstrated to be effective in anti‐tumor. To fully understand its mechanism of action, it is necessary to investigate the in vitro and in vivo metabolic profiles. For in vitro metabolism, H3B‐6545 (50 μM) was incubated with the hepatocytes of rat and human for 2 h. For in vivo metabolism H3B‐6545 was orally administered to rats at a single dose of 10 mg/kg, and plasma, urine and fecal samples were then collected. All samples were analyzed by using ultra‐high performance liquid chromatography combined with linear ion trap‐orbitrap tandem mass spectrometry (UHPLC‐LTQ‐Orbitrap‐MS) operated in positive ion mode. The structures of the metabolites were elucidated by comparing their MS and MS2 spectra with those of parent drug. A total of 11 metabolites, including a GSH adduct, were detected and structurally identified. M2, M7 and M8 were further unambiguously identified by using reference standards. Among these metabolites, M1, M5, M7 and M10 were newly found and reported for the first time. The metabolic pathways of H3B‐6545 included deamination (M8 and M9), dealkylation (M2, M3 and M10), N‐hydroxylation (M6), hydroxylation (M1 and M4), formation of amide derivatives (M5 and M7) and GSH conjugation (G1).

We present a technique to rapid determine taxane in blood samples by supercritical fluid chromatography together with mass spectrometry. The aim of this study was to develop a supercritical fluid chromatography with mass spectrometry method for the analysis of paclitaxel, cabazitaxel, and docetaxel in whole-blood samples of rats. Liquid-dry matrix spot extraction was selected in sample preparation procedure. Supercritical fluid chromatography separation of paclitaxel, cabazitaxel, docetaxel, and glyburide (internal standard) was accomplished within 3 min by using the gradient mobile phase consisted of methanol as the compensation solvent and carbon dioxide at a flow rate of 1.0 mL/min. The method was validated regarding specificity, the lower limit of quantification, repeatability, and reproducibility of quantification, extraction recovery, and matrix effects. The lower limit of quantification was found to be 10 ng/mL since it exhibited acceptable precision and accuracy at the corresponding level. All interday accuracies and precisions were within the accepted criteria of ±15% of the nominal value and within ±20% at the lower limit of quantification, implying that the method was reliable and reproducible. In conclusion, this method is a promising tool to support and improve preclinical or clinical pharmacokinetic studies with the taxanes anticancer drugs.

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