Atractylodis exerted a variety of pharmacological effects such as anti-tumor, anti-inflammatory, anti-bacterial, and anti-aging effects etc. The major ingredients of Atractylodis are atractylenolide I and II that exhibited activities in anti-inflammatory and anticancer. In this work, a sensitive and selective ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method for determination of atractylenolide I and II in rat plasma was developed. The UPLC–MS/MS method was validated for selectivity, linearity, accuracy, precision, recovery, and stability with a total run time of 4.0 min. After addition of atractylenolide III 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 × 50 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 231.1 → 185.1 for atractylenolide I, m/z 233.1 → 91.0 for II, and m/z 249.0 → 231.1 for IS. Calibration plots were linear throughout the range 1–1000 ng/mL for atractylenolide I and II in rat plasma. Mean recoveries of atractylenolide I and II in rat plasma ranged from 86.2% to 96.3%. Relative standard deviation (RSD) of intra-day and inter-day precision was both less than 12%. The accuracy of the method was between 91.0% and 109.0%. The method was successfully applied to pharmacokinetic study of atractylenolide I and II after intravenous administration in rats.
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We developed an ultra-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method for quantification of panasenoside pharmacokinetics in rat plasma and tissue distribution in mouse. Twelve male Sprague-Dawley rats were used for pharmacokinetics after intravenous (2 or 10 mg/kg) administration of panasenoside, six rats for each dose. Thirty mice were randomly divided into six groups (five mice for each group, one group for each time point) and received 20 mg/kg of panasenoside by intraperitoneal administration. Calibration plots were in the range of 2–2000 ng/mL for panasenoside in rat plasma and 2–3000 ng/mL in mouse tissues. The relative standard deviation (RSD) of inter-day and intra-day precision was less than 14%. The accuracy was between 89.6% and 110.0%. The AUC(0-t) was 160.8 ± 13.0 and 404.9 ± 78.0 ng/mL*h, and t1/2 of 3.2 ± 1.2 and 4.6 ± 1.7 h, CL (clearance) of 10.0 ± 2.0, and 21.4 ± 2.0 L/h/kg after intravenous administration 2 mg/kg and 10 mg/kg of panasenoside, respectively. The tissue distribution results indicated that the panasenoside diffuses rapidly and widely into major organs. The level of panasenoside was highest in mouse liver, followed by kidney, lung, and spleen. The overwhelming accumulation in liver indicated that liver was responsible for the extensive metabolism.
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