Dauricine has a variety of pharmacological properties including anti-inflammatory, anti-arrhythmic, and antihypertensive effects as well as reversing multidrug resistance (MDR) of cancer cells. While its therapeutic application is increasing, its bioavailability of different administration routes has not been studied. In the present study, we developed and validated a liquid chromatography/electrospray ionization mass spectrometry method (LC-MS/MS). Using this method, we quantified dauricine in rat plasma after administration via intravenous (i.v.) injection, per oral (p.o.), and intraperitoneal injection (i.p.). Our results indicated that this method detected plasma dauricine with a good linearity in the range of 1.95–1000.00 ng/mL (r = 0.9997). The extraction method showed an average intra- and inter-day recovery of 98.21–104.35% and 98.0–103.58%, respectively. Dauricine showed a fast absorption and widespread distribution after administration in all three tested routes. After intravenous administration (2.5, 5.0, 10.0 mg/kg), the pharmacokinetics of dauricine exhibited a first-order kinetics. In addition, dauricine showed a slow elimination with a long half-life (t1/2z) and double peaks phenomenon following p.o. and i.p. administration. Furthermore, using area under the plasma concentration-time curve (AUC), we calculated absolute bioavailability, which was over twofold higher when administered via i.p. than via p.o. administration. The newly obtained information from our study will provide important reference for dauricine dose and administration route in designing dauricine therapy for applicable diseases.
spectrometry (UPLC–MS/MS) method was established to determine hapepunine in mouse blood, the pharmacokinetics of hapepunine after intravenous and intragastric administration was studied, and the absolutebioavailability was obtained
circulatory system. Clearance, MRT (0 − t ) , and t 1/2 values were estimated at 97.0 ± 28.9 L/h/kg, 0.8 ± 0.1 h, and 0.7 ± 0.2 h, respectively, indicating rapid elimination from the circulatory system in rats. The absolutebioavailability of GAL was 7
Authors:P. Laczay, G. Semjén, J. Lehel, and G. Nagy
The pharmacokinetics and the influence of food on the kinetic profile and bioavailability of doxycycline was studied after a single intravenous (i.v.) and oral dose of 10.0 mg/kg body weight in 7-week-old broiler chickens. Following i.v. administration the drug was rapidly distributed in the body with a distribution half-life of 0.21 ± 0.01 h. The elimination half-life of 6.78 ± 0.06 h was relatively long and resulted from both a low total body clearance of 0.139 ± 0.007 L/h·kg and a large volume of distribution of 1.36 ± 0.06 L/kg. After oral administration to fasted chickens, the absorption of doxycycline was quite fast and substantial as shown by the absorption half-life of 0.39 ± 0.03 h, the maximal plasma concentration of 4.47 ± 0.16 —g/mL and the time to reach the Cmax of 1.73 ± 0.06 h. The distribution and the final elimination of the drug were slower than after i.v. administration. The absolute bioavailability was 73.4 ± 2.5%. The presence of food in the intestinal tract reduced and extended the absorption (t1/2a = 1.23 ± 0.21 h; Cmax = 3.07 ± 0.23 µg/mL; tmax = 3.34 ± 0.21 h). The absolute bioavailability was reduced to 61.1% ± 4.4%.
Authors:Xi Bao, Bingge Huang, Yiting Mao, Zhiguang Zhang, Yunfang Zhou, Congcong Wen, and Quan Zhou
Byakangelicol is one of coumarins from Baizhi and has been shown to inhibit the release of PGE2 from human lung epithelial A549 cells in a dose-dependent manner. A sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method was developed and full validated for the quantification of byakangelicol in rat plasma. The pharmacokinetics of byakangelicol after both intravenous (5 mg/kg) and oral (15 mg/kg) administrations were studied. Chromatographic separation was performed on an ultra-performance liquid chromatography ethylene bridged hybrid (UPLC BEH) C18 column with acetonitrile and 0.1% formic acid as the mobile phase at a flow rate of 0.4 mL/min; fargesin was used as the internal standard (IS). The following quantitative analysis of byakangelicol was utilized in the multiple reaction monitoring mode. The samples were extracted from rat plasma via protein precipitation using acetonitrile. In the concentration range of 1–2000 ng/mL, the method correlated linearity (r > 0.995) with a lower limit of quantitation (LLOQ) of 1 ng/mL. Intra-day precision was less than 11%, and inter-day precision was less than 12%. The accuracy was between 92.0% and 108.7%, the recovery was better than 89.6%, and the matrix effect was between 85.9% and 98.6%. The method was successfully applied to a pharmacokinetic study of byakangelicol after intravenous and oral administration, and the absolute bioavailability was 3.6%.
Palmatine is a compound with good water solubility extracted from Coptis chinensis, Fibraurea recisa Pierre, Cortex Phellodendri Chinensis. Palmatine has good antibacterial activity and mainly used for the treatment of bacterial dysentery, gynecological inflammation, surgical infection, and conjunctivitis. It has anti-diabetic, anti-oxidant, and cognitive-enhancing activities. In this study, we used UPLC-MS/MS to determinate palmatine in rat plasma, and investigated its pharmacokinetics. Coptisine was utilized as an internal standard (IS), and acetonitrile precipitation method was used to process the plasma samples. Chromatographic separation was achieved using a UPLC BEH C18 column using mobile phase of acetonitrile- 0.1% formic acid with gradient elution. Electrospray ionization (ESI) tandem mass spectrometry in multiple reaction monitoring (MRM) mode with positive ionization was applied. The results indicated that within the range of 1–500 ng/mL, linearity of palmatine in rat plasma was acceptable (r > 0.995), and the lower limit of quantification (LLOQ) was 1 ng/mL. Intra-day and inter-day precision RSD of palmatine in rat plasma were less than 14%. Accuracy range was between 93.7 and 107.1%, and matrix effect was between 101.6 and 109.4%. The method was successfully applied in the pharmacokinetics of palmatine in rats after oral and intravenous administration. The absolute bioavailability of the palmatine was 15.5% in rats.
Authors:Meifei Lu, Xiaojie Lu, Zheng Yu, and Congcong Wen
Calycanthine is an important class of alkaloids extracted and isolated from the roots, leaves, flowers and fruits of Chimonanthus praecox. In this work, the UPLC-MS/MS method was used for determination of calycanthine in rat plasma, and the pharmacokinetics in rats were investigated. Midazolam was used as an internal standard (IS), and methanol precipitation method was used to pretreatment the rat plasma samples. Chromatographic separation was achieved on a UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column with the mobile phase of methanol- 0.1% formic acid aqueous solution with gradient elution. Multiple reaction monitoring (MRM) mode with positive ionization was applied for quantitative analysis, m/z 347.3 → 246.7 and 326.2 → 291.4 for calycanthine and IS, respectively. The results indicated that within the range of 1–200 ng/mL, linearity of calycanthine in rat plasma was good (r > 0.995), and the lower limit of quantification (LLOQ) was 1 ng/mL. Accuracy range was between 90.6 and 109.4%, precision (RSD) of calycanthine was less than 14%. The matrix effect was between 97.9% and 105.4%, the recovery was better than 85.6%. The developed UPLC-MS/MS method was successfully applied in the pharmacokinetics of calycanthine in rats after oral and intravenous administration. The absolute bioavailability of the calycanthine was 37.5% in rats.
Authors:Jing Zhou, Hongzhe Wang, Caiyun Miao, Yunxi Yao, and Jianshe Ma
A rapid and simple UPLC-MS/MS method was developed to determine toddalolactone in mouse blood and applied to measure the pharmacokinetics of toddalolactone in mice. Blood samples were first preprocessed by ethyl acetate liquid-liquid extraction. Oxypeucedanin hydrate (internal standard, IS) and toddalolactone were gradient eluted from a UPLC BEH C18 column using a mobile phase consisting of acetonitrile and water (0.1% formic acid). Using electrospray ionization (ESI) as the ionization source, multiple reaction monitoring was used to detect the precursor and product ions of m/z 309.2 and 205.2, respectively, for toddalolactone and of m/z 305.1 and 203.0 for IS, respectively, for quantitative detection. A calibration curve was run over the concentration range of 5–4,000 ng/mL (r > 0.995). The matrix effects ranged from 93.5 to 98.4%, and the recovery was higher than 77.3%. The precision was less than 13%, and the accuracy ranged from 90.9 to 108.4%. The developed UPLC-MS/MS method was successfully used for measuring the pharmacokinetics of toddalolactone in mice after oral (20 mg/kg) and intravenous administration (5 mg/kg), and the absolute bioavailability of toddalolactone was 22.4%.
Authors:L. Galgóczy, Liliána Tóth, M. Virágh, T. Papp, and Cs. Vágvölgyi
, C. (2007) Pharmacokinetics and absolutebioavailability of selegiline following treatment of healthy subjects with the selegiline transdermal system (6 mg/24 h): a comparison with oral selegiline capsules. J. Clin. Pharmacol. 47 , 1256