The UHPLC-MS/MS determination and pharmacokinetic study of three active compounds in male rats after oral administration of Saxifraga stolonifera (L.) Meerb extract

2016 ◽  
Vol 8 (12) ◽  
pp. 2604-2612
Author(s):  
Yanfang Yan ◽  
Xiaojian Gong ◽  
Xin Zhou ◽  
Sushan Lyu ◽  
Zhengmeng Jiang ◽  
...  
Keyword(s):  
Oral Administration ◽  
Pharmacokinetic Study ◽  
Male Rats ◽  
Bioactive Components ◽  
Active Compounds ◽  
Pharmacokinetic Properties

Saxifraga stolonifera (S. stolonifera) has been used to cure various diseases effectively while little is known about the pharmacokinetic properties of the bioactive components of S. stolonifera.

scholarly journals Effect of Ticagrelor, a Cytochrome P450 3A4 Inhibitor, on the Pharmacokinetics of Tadalafil in Rats

Pharmaceutics ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 354 ◽  
Author(s):  
Young-Guk Na ◽  
Jin-Ju Byeon ◽  
Hyun Wook Huh ◽  
Min-Ki Kim ◽  
Young G. Shin ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Oral Administration ◽  
Systemic Exposure ◽  
Compartment Model ◽  
Male Rats ◽  
Combination Regimen ◽  
Sprague Dawley ◽  
Pharmacokinetic Properties ◽  
Pretreated Group ◽  
Few Data

Tadalafil is a cytochrome P450 (CYP) 3A4 substrate. Because there are few data on drug-drug interactions, it is advisable to take sufficient consideration when co-administering tadalafil with CYP3A4 inducers or inhibitors. This study was conducted to assess the effect of ticagrelor, a CYP3A4 inhibitor, on the pharmacokinetic properties of tadalafil after oral administration to rats. A total of 20 Sprague–Dawley male rats were randomly divided into the non-pretreated group and ticagrelor-pretreated group, and tadalafil was orally administered to each group after pretreatment with or without ticagrelor. Blood samples were collected at predetermined time points after oral administration of tadalafil. As a result, systemic exposure of tadalafil in the ticagrelor-pretreated group was significantly increased compared to the non-pretreated group (1.61-fold), and the clearance of tadalafil in the ticagrelor-pretreated group was significantly reduced than the non-pretreated group (37%). The prediction of the drug profile through the one-compartment model could explain the differences of pharmacokinetic properties of tadalafil in the non-pretreated and ticagrelor-pretreated groups. This study suggests that ticagrelor reduces a CYP3A-mediated tadalafil metabolism and that tadalafil and a combination regimen with tadalafil and ticagrelor requires dose control and specific pharmacotherapy.

scholarly journals Identification and pharmacokinetics of saponins in Rhizoma Anemarrhenae after oral administration to rats by HPLC-Q-TOF/MS and HPLC-MS/MS

2021 ◽  
Vol 71 (4) ◽  
pp. 567-585
Author(s):  
Hai-Qiao Wang ◽  
Fen Lan ◽  
Yi-Han Zhang ◽  
Jin-Er Xia ◽  
Xiao-Mei Gong ◽  
...  
Keyword(s):  
Herbal Medicine ◽  
Oral Administration ◽  
Pharmacokinetic Study ◽  
Matrix Effect ◽  
Plasma Concentrations ◽  
Rat Plasma ◽  
Bioactive Components ◽  
Elimination Half ◽  
Intended Use ◽  
Tof Ms

Abstract Rhizoma Anemarrhenae is a well-known herbal medicine with saponins as its commonly regarded major bioactive components. It is essential to classify the properties of saponins which are associated with their toxicity and efficacy. In this study, 25 compounds were identified by HPLC-Q-TOF/MS in the extract of Rhizoma Anemarrhenae and 8 saponins were detected in rat plasma by HPLC-MS/MS after oral administration of this extract. These were neomangiferin, mangiferin, timosaponin E1, timosaponin E, timosaponin B-II, timosaponin B-III, timosaponin A-III and timosaponin A-I. A sensitive and accurate HPLC-MS/MS method was developed and successfully applied to a pharmacokinetic study of the abovementioned eight saponins after oral administration of the Rhizoma Anemarrhenae extract to rats. The method validation, including specificity, linearity, precision, accuracy, recovery, matrix effect and robustness, met the requirements of the intended use. The pharmacokinetic parameter, T max value, ranged from 2 to 8 h for these eight saponins whereas their elimination half-life (t 1/2) ranged from 4.06 to 9.77 h, indicating slow excretion. The plasma concentrations of these eight saponins were all very low, indicating a relatively low oral bioavailability. All these results provide support for further clinical studies.

Development and validation of a LC-MS/MS method for quantification of mobocertinib (TAK-788) in plasma and its application to pharmacokinetic study in rats

2020 ◽  
Vol 23 ◽  
Author(s):  
Bo Li ◽  
Jin Wang ◽  
Xinyao Dou ◽  
Xinjie Zhang ◽  
Xianbei Xue ◽  
...  
Keyword(s):  
Oral Administration ◽  
Pharmacokinetic Study ◽  
High Performance ◽  
Kinase Inhibitor ◽  
Internal Standard ◽  
Selected Reaction Monitoring ◽  
Precipitation Method ◽  
Plasma Samples ◽  
Bioanalytical Method Validation ◽  
Extraction Recovery

Aim and Objective:: An analytical method for the determination of mobocertinib, an investigational tyrosine kinase inhibitor, was developed and optimized by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) in rat plasma. Materials and Methods:: Plasma samples were pretreated by the protein precipitation method with a methanol solution of osimertinib as the internal standard (IS). Chromatographic separation was performed using an Inertsil ODS-3 column (50 mm × 4.6 mm, I.D. 5 μm) column with the temperature maintained at 40 °C. The mobile phase consisted of water (containing 0.1% formic acid) and methanol in a gradient mode at a flow rate of 0.5 mL/min. Mass spectrometric detection was carried out in the selected reaction monitoring (SRM) mode with positive electrospray ionization, and the mass transitions of mobocertinib and osimertinib were m/z 587.01 → 71.88 and m/z 499.80 → 71.94, respectively. The method was validated in terms of selectivity, linearity, accuracy and precision, extraction recovery and matrix effect, stability and carryover as per the guidelines for bioanalytical method validation (FDA, 2018). The method was applied to the pharmacokinetic study of mobocertinib in rats by oral gavage at the doses of 2, 6, and 18 mg/kg. A total of 216 plasma samples from 18 rats were analyzed. Results:: It showed good linearity over the range of 1-1000 ng/mL (R2 = 0.9957). The intra-batch accuracy was within 94.65-102.59% and the precision was within 5.49-10.46%. The inter-batch accuracy was within 97.08-102.25% with a precision of 7.54-10.13%. The extraction recovery and matrix factor were acceptable for the bioanalysis of mobocertinib. Additionally, mobocertinib was found to be stable under the detected conditions. Mobocertinib showed linear pharmacokinetic characteristics following oral administration to rats at 2.0-18.0 mg/kg. Conclusion:: The developed and validated method was successfully employed in the pharmacokinetic study in rats following oral administration of mobocertinib at the doses of 2, 6, and 18 mg/kg.

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