Liquid Chromatography-Tandem Mass Spectrometry Method for Ticagrelor and its Active Metabolite Determination in Human Plasma: Application to a Pharmacokinetic Study

2020 ◽  
Vol 16 (5) ◽  
pp. 602-608
Author(s):  
Niloufar Marsousi ◽  
Serge Rudaz ◽  
Jules A. Desmeules ◽  
Youssef Daali
Keyword(s):  
Clinical Trial ◽  
Formic Acid ◽  
Human Plasma ◽  
Active Metabolite ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Healthy Male ◽  
Coronary Syndrome ◽  
Healthy Male Volunteers ◽  
Male Volunteers

Background: Ticagrelor is a highly recommended new antiplatelet agent for the treatment of patients with acute coronary syndrome at moderate or high ischemic risk. There is a real need for rapid and accurate analytical methods for ticagrelor determination in biological fluids for pharmacokinetic studies. In this study, a sensitive and specific LC-MS method was developed and validated for quantification of ticagrelor and its Active Metabolite (AM) in human plasma over expected clinical concentrations. Methods: Samples were handled by Liquid-Liquid Extraction (LLE). A linear gradient was applied with a mobile phase composed of formic acid 0.1% and acetonitrile with 0.1% of formic acid using a C18 reversed-phase column. MS spectra were obtained by electrospray ionization in negative mode and optimized at 521.4→360.9 m/z, 477.2→361.2 m/z and 528.1→367.9 m/z transitions for ticagrelor, AM and ticagrelor-d7, respectively. Results: This method allowed rapid elution, in less than 4 minutes, and quantification of concentrations as low as 2 ng/mL for ticagrelor and 1 ng/mL for AM using only 100 μL of human plasma. LLE using hexane/ethyl acetate (50/50) was an optimal compromise in terms of extraction recovery and endogenous compounds interference. Trueness values of 87.8% and 89.5% and precisions of 84.1% and 93.8% were obtained for ticagrelor and AM, respectively. Finally, the usefulness of the method was assessed in a clinical trial where a single 180 mg ticagrelor was orally administered to healthy male volunteers. Pharmacokinetic parameters of ticagrelor and its active metabolite were successfully determined. Conclusion: A sensitive and specific quantification LC-MS-MS method was developed and validated for ticagrelor and its active metabolite determination in human plasma. The method was successfully applied to a clinical trial where a single ticagrelor 180 mg dose was orally administered to healthy male volunteers. The described method allows quantification of concentrations as low as 2 ng/mL of ticagrelor and 1 ng/mL of the metabolite using only 100 μL of plasma.

scholarly journals Metabolism and disposition of pyrotinib in healthy male volunteers: covalent binding with human plasma protein

2018 ◽  
Vol 40 (7) ◽  
pp. 980-988 ◽  
Author(s):  
Jian Meng ◽  
Xiao-yun Liu ◽  
Sheng Ma ◽  
Hua Zhang ◽  
Song-da Yu ◽  
...  
Keyword(s):  
Human Plasma ◽  
Plasma Protein ◽  
Covalent Binding ◽  
Healthy Male ◽  
Human Plasma Protein ◽  
Healthy Male Volunteers ◽  
Male Volunteers

A Phase I clinical trial of lodenafil carbonate, a new phosphodiesterase Type 5 (PDE5) inhibitor, in healthy male volunteers

2012 ◽  
Vol 50 (12) ◽  
pp. 896-906 ◽  
Author(s):  
Gustavo D. Mendes ◽  
Hilton Oliveira dos Santos Filho ◽  
Alberto dos Santos Pereira ◽  
Fabiana D. Mendes ◽  
Jaime O. Ilha ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Pde5 Inhibitor ◽  
Phase I Clinical Trial ◽  
Healthy Male ◽  
Healthy Male Volunteers ◽  
Male Volunteers ◽  
Phosphodiesterase Type

scholarly journals Assessment of the Effect of Mefloquine on Artesunate Pharmacokinetics in Healthy Male Volunteers

2006 ◽  
Vol 51 (3) ◽  
pp. 1099-1101 ◽  
Author(s):  
Timothy M. E. Davis ◽  
Michelle England ◽  
Anne-Marie Dunlop ◽  
Madhu Page-Sharp ◽  
Nathalie Cambon ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Active Metabolite ◽  
Healthy Male ◽  
Time Curve ◽  
Concentration Time ◽  
Healthy Male Volunteers ◽  
Male Volunteers

ABSTRACT The effect of mefloquine on artesunate pharmacokinetics was assessed in 20 volunteers given artesunate for 3 days, followed ≥21 days later by combination therapy for 3 days. The areas under the concentration-time curve from 0 h to infinity for dihydroartemisinin, the active metabolite of artesunate, were similar on day 3 of the two dosing periods (P = 0.12), implying no interaction.

scholarly journals Pharmacokinetic Parameters of Ciprofloxacin in Bangladeshi Volunteers: A Preliminary Evaluation

2014 ◽  
Vol 27 (1-2) ◽  
pp. 1-8
Author(s):  
Reefat Zaman Chowdhury ◽  
Md Saiful Islam ◽  
Md Sayedur Rahman
Keyword(s):  
Healthy Volunteers ◽  
Oral Route ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Intravenous Route ◽  
Population Pharmacokinetic ◽  
Healthy Male ◽  
Healthy Male Volunteers ◽  
Male Volunteers ◽  
The Difference

The present study has attempted to establish a High-performance liquid chromatography (HPLC) method to determine ciprofloxacin in plasma, in order to evaluate the bioavailability of ciprofloxacin. In this study, initially 8 (eight) Bangladeshi Bangalee healthy male volunteers and 7 (seven) Bangladeshi Tribal healthy male volunteers received 500 mg tablet of pioneer brand of ciprofloxacin in oral route. Blood samples were collected at 0, 30, 60, 120, 180, 360, 540 and 720 minutes after drug administration. After 1 week of washout period, same volunteers of two groups received 200 mg injection of pioneer brand of ciprofloxacin in intravenous route. HPLC with ultraviolet detection was used to quantify plasma ciprofloxacin concentrations. In case of oral route, AUC0–12h, Cmax, Tmax and T1/2 values for Bangladeshi Bangalee and Tribal healthy volunteers were 545.53 ± 32.35 & 655.74 ± 16.57 ?g min/mL, 2.19 ± 0.16 & 2.49 ± 0.20 ?g/mL, 75.00 ± 27.77 & 94.29 ± 32.07 min and 241.96 ± 13.53 & 242.02 ± 19.88 min respectively. In case of intravenous route, the AUC0–12h, Cmax, Tmax and T1/2 values for Bangladeshi Bangalee and Tribal healthy volunteers were 344.07 ± 29.31 & 343.31 ± 25.34 ?g min/mL, 2.47 ± 0.17 & 2.46 ± 0.18 ?g/mL, 30.00 ± 0.00 & 30.0 ± 0.0 min and 278.16 ± 1.74 & 272.74 ± 4.42 min respectively and the difference between these two groups of volunteers was not significant. The difference in AUC0–12h, Cmax, Tmax and T1/2 values between these two groups of volunteers was significant. The mean percent absolute bioavailability in Bangladeshi Bangalee and Tribal healthy volunteers was 64.04 ± 3.21 and 76.81 ± 6.71 respectively. In conclusion, pharmacokinetic parameters of ciprofloxacin significantly varied among Bangladeshi Bangalee and Bangladeshi Tribal healthy volunteers indicating necessity of further study on population pharmacokinetic in these groups of people. DOI: http://dx.doi.org/10.3329/bjpp.v27i1-2.20066 Bangladesh J Physiol Pharmacol 2011;27(1&2):1-8.

scholarly journals A pharmacokinetics study of proposed bevacizumab biosimilar MYL-1402O vs EU-bevacizumab and US-bevacizumab

2021 ◽  
Author(s):  
Matthew Hummel ◽  
Tjerk Bosje ◽  
Andrew Shaw ◽  
Mark Shiyao Liu ◽  
Abhijit Barve ◽  
...  
Keyword(s):  
Serum Concentration ◽  
Phase 1 ◽  
Elimination Rate ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Healthy Male ◽  
Double Blind ◽  
Healthy Male Volunteers ◽  
Male Volunteers ◽  
Eu And Us

Abstract Purpose Bevacizumab is a recombinant humanized monoclonal antibody that inhibits vascular endothelial growth factor-specific angiogenesis in some cancers. MYL-1402O is a proposed bevacizumab biosimilar. Methods The primary objective of this single-center, randomized, double-blind, three-arm, parallel-group, phase 1 study in healthy male volunteers was to evaluate bioequivalence of MYL-1402O to EU and US-reference bevacizumab, and EU-reference bevacizumab to US-reference bevacizumab. The primary pharmacokinetic parameter was area under the serum concentration–time curve from 0 extrapolated to infinity (AUC0–∞). Pharmacokinetic parameters were analyzed using general linear models of analysis of variance. Secondary endpoints included safety and tolerability. Results Of 111 enrolled subjects, 110 were included in the pharmacokinetic analysis (MYL-1402O, n = 37; EU-reference bevacizumab, n = 36; US-reference bevacizumab, n = 37). Bioequivalence was demonstrated between MYL-1402O and EU-reference bevacizumab, MYL-1402O and US-reference bevacizumab, and between EU- and US-reference bevacizumab where least squares mean ratios of AUC0–∞ were close to 1, and 90% CIs were within the equivalence range (0.80–1.25). Secondary pharmacokinetic parameters (AUC from 0 to time of last quantifiable concentration [AUC0–t], peak serum concentration [Cmax], time to Cmax, elimination rate constant, and elimination half-life) were also comparable, with 90% CIs for ratios of AUC0–t and Cmax within 80–125%. Treatment-emergent adverse events were similar across all three treatment groups and were consistent with clinical data for bevacizumab. Conclusion MYL-1402O was well tolerated and demonstrated pharmacokinetic and safety profiles similar to EU-reference bevacizumab and US-reference bevacizumab in healthy male volunteers. No new significant safety issues emerged (ClinicalTrials.gov, NCT02469987; ClinicalTrialsRegister.eu EudraCT, 2014-005621-12; June 12, 2015).

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