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R-/S-2-(2-Hydroxypropanamido) benzoic acid (R-/S-HPABA), a marine-derived anti-inflammatory drug, however, the antiplatelet and antithrombotic effects have not been investigated. In this paper, the in vitro antiplatelet activities and in vivo antithrombotic effects of R-/S-HPABA were investigated, for the first time. The effects of R-/S-HPABA on platelet aggregation induced by adenosine diphosphate (ADP), collagen (COLL) and arachidonic acid (AA) were evaluated. In addition, the in vivo bleeding time, clotting time, collagen-epinephrine induced pulmonary thrombosis and common carotid artery thrombosis were also investigated in rats. R-/S-HPABA significantly inhibited ADP, COLL and AA induced platelet aggregation in rabbit platelet rich plasma in vitro compared with control group, to a degree similar to that of aspirin. Besides, R-/S-HPABA prolonged bleeding time and clotting time as well as increased the recovery rate obviously in pulmonary thrombosis. Moreover, the level of thromboxane B2 (TXB2) was decreased while the production of 6-keto-prostaglandin F1α (6-keto-PGF1α) was increased markedly by R-/S-HPABA. Furthermore, R-/S-HPABA reduced carotid artery thrombosis weight. These results illustrated that R-/S-HPABA could be a potent antiplatelet aggregation and antithrombotic agent. [ABSTRACT FROM AUTHOR]

Highlights: [•] Development of a UHPLC–MS/MS method to determine HPABA in rat plasma. [•] The total analysis time was 2.0min. [•] The method was applied to pharmacokinetic study of HPABA in rats. [•] HPABA showed linear pharmacokinetic properties and high absolute bioavailability. [ABSTRACT FROM AUTHOR]

Highlights: [•] Simultaneous determination of puerarin glucuronide, puerarin and daidzin in rat plasma. [•] An UPLC–MS/MS method was developed and applied for pharmacokinetic study. [•] Comparative pharmacokinetics was performed in rats under different physiological states. [•] Blood stasis syndrome had effect on pharmacokinetics of puerarin glucuronide, puerarin and daidzin. [•] Pharmacokinetics of the three constituents changed when Gegen was used in combination with Sanqi. [Copyright &y& Elsevier]

Abstract: In order to investigate the preclinical pharmacokinetics of cefuroxime lysine, a fast, sensitive and high throughput UPLC–ESI–MS/MS method has been developed and validated for the quantitative determination of cefuroxime in dog plasma. Cefuroxime and IS phenacetin were extracted from plasma samples by PPT or LLE procedure, and then separated on an ACQUITY UPLC™ BEH C18 column with an isocratic elution of acetonitrile–0.1% formic acid in 10mM ammonium acetate (40:60, v/v). MRM using the fragmentation transitions of m/z 442→364 and 180→110 in positive ESI mode was performed to quantify cefuroxime and IS, respectively. The calibration curves were linear over the concentration range of 2–400μg/ml for PPT and 0.01–5μg/ml for LLE. The LLOQ was 0.01μg/ml. The intra- and inter-day precisions in all samples were no more than 8.1%, while the accuracy was within ±6.2% of nominal values. The method was successfully applied to the evaluation of pharmacokinetic parameters of cefuroxime lysine in beagle dogs. [Copyright &y& Elsevier]

A high-performance liquid chromatography tandem mass spectrometry (HPLC–MS/MS) method was developed and fully validated for simultaneous determination of puerarin, 3′-hydroxy puerarin, 6″- O -xylosyl puerarin, 3′-methoxy puerarin, mirificin, puerarin-7- O -glucoside, daidzin, daidzein, daidzein-7- O -glucoside, ginsenoside-Rd, notoginsenoside-R1, ginsenoside-Re, ginsenoside-Rg1, ginsenoside-Rb1 in rat plasma after intravenous injection of 5 mL/kg Gegen-Sanqi compatibility solution (containing Pueraria flavonid 10.8 mg/mL and Panax notoginsenosidum 5.4 mg/mL). After addition of internal standard (IS) baicalin, the analytes and IS were recovered from rat plasma by protein precipitation using acetonitrile containing 0.1% formic acid. Chromatographic separation was performed on a Capcell pak MG C18 column (3.0 mm × 75 mm, 3.0 μm) at 35 °C with a flow rate of 0.75 mL/min. Mass spectrometry was conducted using multiple reaction monitoring in positive mode. The method was linear for all of the analytes over 1000 times concentration range with correlation coefficients greater than 0.99. The precision and accuracy of the LC–MS/MS assay based on the three analytical quality control (QC) levels were well within the acceptance criteria from FDA guidance for bioanalytical method validation. Method recoveries were higher than 75% and the matrix effects were minimal. All analytes were stable under tested conditions. It was the first time to study the pharmacokinetics of daidzein-7- O -glucoside in rat plasma. To the best of our knowledge, this is the first study for simultaneous determination of so many analytes in rat plasma after intravenous injection of Gegen-Sanqi compatibility solution. It was expected that the present work would provide some helpful references for the apprehension of the mechanism of action and further clinical efficacy studies of Gegen-Sanqi herb-pair. [ABSTRACT FROM AUTHOR]

Rapid, sensitive, selective and accurate UPLC–MS/MS method was developed and fully validated for simultaneous determination of cinnamaldehyde, cinnamic acid, 2-methoxy cinnamic acid, glycyrrhizic acid, glycyrrhetinic acid, liquiritigenin and isoliquiritin in rat plasma after oral administration of Guizhi-gancao decoction. Plasma samples were processed with a simple protein precipitation technique using acetonitrile, followed by chromatographic separation using a Thermo Hypersil GOLD C 18 column. A 11.0 min linear gradient elution was used at a flow rate of 0.2 mL/min with a mobile phase of 0.1% acetic acid containing 0.2 mM ammonium acetate in water and acetonitrile. The analytes and internal standard, schisandrin, were detected using both positive and negative ion electrospray ionization in multiple reaction monitoring mode. The developed method was validated for intra-day and inter-day accuracy and precision whose values fell in the acceptable limits. Matrix effect was found to be minimal. Recovery efficiency of all the analytes was found to be >60%. Stability results showed that the analytes were stable at all the conditions. This validated method was successfully used to study the pharmacokinetics of multiple compounds in rat plasma after oral administration of Guizhi-gancao decoction. [ABSTRACT FROM AUTHOR]

In order to investigate the pharmacokinetics of triamcinolone acetonide palmitate (TAP) which is a lipid-soluble prodrug of triamcinolone acetonide (TA), a rapid, simple, sensitive and reproducible UPLC-MS/MS method has been developed and validated for the simultaneous determination of TAP and TA in beagle dog plasma. After simple liquid–liquid extraction, the analytes and internal standard (dexamethasone, DEX) were separated on Phenomenex Luna C 18 column (50 mm × 2.1 mm, 1.7 μm) using a mobile phase consisting of solvent A (acetonitrile) and solvent B (0.1% ammonia solution) at a flow rate of 0.2 ml/min with gradient elution. Acquisition of mass spectrometric data was performed in multiple reaction monitoring (MRM) mode via positive electrospray ionization using the ion transitions of m/z 673.5 → 397.3, 435.3 → 415.3 and 393.3 → 355.3 for TAP, TA and IS, respectively. The method was of satisfactory specificity, sensitivity, precision and accuracy over the concentration range of 1–1000 ng/ml for TAP and 0.5–500 ng/ml for TA. The intra- and inter-day precisions for both TAP and TA were 3.2% to 18.7% and the accuracy was in the range of −8.4% to 6.8%. The mean recoveries of TAP, TA and IS were 86.7–104.7%. The method was successfully applied to a long-term pharmacokinetic study of TAP and TA after 28-day repeated intravenous administration of TAP lipid emulsion injection to beagle dogs. [ABSTRACT FROM AUTHOR]

Highlights: [•] The report describes the validation of a high precision and accuracy UPLC–MS/MS method for the simultaneous determination of limonin, dictamnine, obacunone and fraxinellone in rat plasma. [•] The pharmacokinetic study of Cortex Dictamni in rats is firstly reported. [•] Extraction performed with a simple liquid–liquid extraction. [•] Sensitivity, specificity and high throughput. [Copyright &y& Elsevier]