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Pan P.-P.,Taizhou Central Hospital | Wang S.-H.,The Laboratory of Clinical Pharmacy | Wang J.,Wenzhou University | Luo J.,Maternal and Child Health Hospital of Taizhou | And 3 more authors.
Chromatographia | Year: 2016

A sensitive and rapid ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed to determine methadone, EDDP, fluoxetine, norfluoxetine, venlafaxine and O-desmethylvenlafaxine in rat plasma using diazepam as the internal standard (IS). Sample preparation was accomplished through a simple one-step protein precipitation with 200 µL acetonitrile added to 100 µL rat plasma. The analytes were separated on an Acquity UPLC BEH C18 column (2.1 × 50 mm, 1.7 µm) and the mobile phase was acetonitrile and 0.1 % formic acid in water in gradient elution at a flow rate of 0.40 mL min−1. The detection was performed on a triple quadrupole tandem mass spectrometer equipped with positive electrospray ionization (ESI) by multiple reactions monitoring (MRM) of the transitions. The linearity of this method was found to be within the concentration range of 0.5–250.0 ng mL−1 for methadone, EDDP, fluoxetine and norfluoxetine and 0.4–200.0 ng mL−1 for venlafaxine and O-desmethylvenlafaxine, respectively. The limit of quantification (LOQ) was 0.5 ng mL−1 for methadone, EDDP, fluoxetine and norfluoxetine and 0.4 ng mL−1 for venlafaxine and O-desmethylvenlafaxine, respectively. A time period of 3 min was needed for an analytical run. The method described above was successfully applied to the subsequent pharmacokinetic study. © 2016 Springer-Verlag Berlin Heidelberg

Chen S.,Wenzhou Central Hospital | Jia Z.,Wenzhou Central Hospital | Dong L.,Wenzhou University | Geng P.,The Laboratory of Clinical Pharmacy | And 4 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2015

Angeloylgomisin H, as a major lignin in the fruits, was reported to have the potential to improve insulin-stimulated glucose uptake by activating PPAR-γ. In this work, a sensitive and selective UPLC-MS/MS method for determination of angeloylgomisin H in rat plasma is developed. After addition of rutin as an internal standard (IS), protein precipitation by acetonitrile was used to prepare samples. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 μm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 523.2-315.1 for angeloylgomisin H, and m/z 611.1-303.1 for IS. Calibration plots were linear throughout the range 5-2000 ng/mL for angeloylgomisin H in rat plasma. Mean recoveries of angeloylgomisin H in rat plasma ranged from 86.2% to 92.5%. RSD of intra-day and inter-day precision were both < 11%. The accuracy of the method was between 93.0% and 104.1%. The method was successfully applied to pharmacokinetic study of angeloylgomisin H after either oral or intravenous administration. The absolute bioavailability of angeloylgomisin H was reported as high as 4.9%. © 2015, E-Century Publishing Corporation. All rights reserved.

Chen L.,Wenzhou Peoples Hospital | Cai J.,Wenzhou University | Wang S.,The Laboratory of Clinical Pharmacy | Hu L.,Wenzhou University | Yang X.,Wenzhou University
International Journal of Clinical and Experimental Medicine | Year: 2015

Kushen (Radix Sophorae Flavescentis) is the dried roots of Sophora Flavescens Ait, alkaloids and flavonoids are the main active constituents of Radix Sophorae Flavescentis. The influence of Radix Sophorae Flavescentis on the activities of CYP450 isoforms CYP2B6, CYP2C19, CYP1A2, CYP2C9, CYP3A4 and CYP2D6 were evaluated by cocktail method. The rats were randomly divided into Radix Sophorae Flavescentis group and control group. The Radix Sophorae Flavescentis group rats were given 5 g/kg Radix Sophorae Flavescentis decoction by intragastric administration. The six probe drugs (bupropion, omeprazole, phenacetin, tolbutamide, midazolam and metroprolol) were given to rats through intragastric administration, and the plasma concentration were determined by UPLC-MS/MS. The result of Radix Sophorae Flavescentis group compared to control group, there were statistical pharmacokinetics difference for omeprazole, phenacetin, tolbutamide and metroprolol. It indicated that the Radix Sophorae Flavescentis may induce the activities of CYP2D6, and inhibit of CYP2C19, CYP1A2 and CYP2C9 of rats. As other drugs are always used after Radix Sophorae Flavescentis, interactions between other drugs and Radix Sophorae Flavescentis undertake the risk of either diminished efficacy or adverse effects. This may give advising for reasonable drug use after Radix Sophorae Flavescentis. © 2015 E-Century Publishing Corporation. All rights reserved.

Wang X.,Wenzhou University | Wang S.,The Laboratory of Clinical Pharmacy | Lin F.,Wenzhou University | Zhang Q.,Shanghai Institute of Pharmaceutical Industry | And 4 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2015

Cabozantinib (XL184) is a novel small molecule inhibitor of receptor tyrosine kinases (RTKs) targeted at mesenchymal-epithelial transition factor (MET). In order to study the pharmacokinetics and tissue distribution in rat, a specific ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed with midazolam as internal standard. The calibration curves in plasma and tissues were linear in the range of 5-5000ng/mL (r2>0.99). The recoveries were better than 80.4% and matrix effects ranged from 96.9% to 105.1%. Then, the developed UPLC-MS/MS method was applied to determine the concentration of XL184 in blood and tissues. The pharmacokinetics of four different dosages (iv 5, 10mg/kg and ig 15, 30mg/kg) revealed that XL184 was eliminated slowly, the t1/2 was longer than 10h and the absolute bioavailability was 25.6±8.3%. The concentration distribution of XL184 in tissues was liver>lung>kidney>spleen>heart. Based on the concentration-time of XL184 in tissues, a BP-ANN distribution model was developed with good performance, and can be used to predict the concentration of XL184 in tissues. © 2015 Elsevier B.V.

Li J.,Wenzhou University | Wang L.,Wenzhou University | Wang S.,The Laboratory of Clinical Pharmacy | Chen M.,Wenzhou University | And 3 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2015

A rapid-resolution ultra high-performance liquid chromatography-tandem mass spectrometry separation method (UPLC-MS/MS) was developed for the simultaneous determination of carvedilol, and its three metabolites: 4'-hydroxyphenyl-carvedilol, 5'-hydroxyphenyl-carvedilol, o-desmethyl-carvedilol. The effective UPLC-MS/MS separation of the examined compounds was applied on an Acquity BEH C18 column (2.1. mm. ×. 50. mm, 1.7. μm particle size) column with a gradient mobile phase system. The analysis was performed in less than 6. min with a flow rate of 0.4. mL/min. The assay was validated over concentration ranges of 0.500-100. ng/mL for carvedilol and 0.0500-10.0. ng/mL for its three metabolites. Intra- and inter-assay precision values for replicate quality control samples were within 11.4% for all analytes during the assay validation. Mean quality control accuracy values were within ±11.5% of nominal values for all analytes. Assay recoveries were high (>91%) and internal standard normalized matrix effects were minimal. The four analytes were stable in rat plasma for at least 24. h at room temperature, 89 days at -20. °C and -80. °C, and following at least five freeze-thaw cycles. The validated assay was successfully applied to the quantification of carvedilol and its pharmacologically active metabolites in rat pharmacokinetic study. The accurate and simple method we developed could be applied to human pharmacokinetic study in the near future. © 2014 Elsevier B.V.

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