An HPLC-MS/MS Method for the Quantitative Determination of Ticagrelor and its Active Metabolite AR-C124910XX in Human Plasma and its Application to a Clinical Study

Peng, Jing-Bo; Wang, Yicheng; Li, Mu-Peng; He, Chenjie; Chen, Yao; Chen, Xiaoping; Ouyang, Dongsheng; Huang, Yuanfei; Tan, Zhijun

doi:10.2174/1573412912666160518151458

Cited by 8 publications

(6 citation statements)

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“…Ticagrelor and AR‐C124910XX were quantified by both positive and negative ionization modes using LC–MS/MS methods (Peng et al, ; Sillén et al, ). In the present study, the ionization of ticagrelor and AR‐C124910XX was tested in both ionization modes in the ESI source.…”

Section: Resultsmentioning

confidence: 99%

“…A limited number of LC–MS/MS methods have been developed and applied to investigate the pharmacokinetics of ticagrelor and its active metabolite AR‐C124910XX after administration of ticagrelor (Peng et al, ; Sillén, Cook, & Davis, ; Sillén, Cook, & Davis, ; Zhong et al, ). However, most of the reported methods have adopted complex liquid–liquid extraction to purify plasma samples (Peng et al, ; Zhong et al, ). Moreover, some methods did not seem sensitive enough for pharmacokinetic studies for low doses of ticagrelor (≤90 mg) (Peng et al, ; Sillén et al, ; Sillén et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…However, most of the reported methods have adopted complex liquid–liquid extraction to purify plasma samples (Peng et al, ; Zhong et al, ). Moreover, some methods did not seem sensitive enough for pharmacokinetic studies for low doses of ticagrelor (≤90 mg) (Peng et al, ; Sillén et al, ; Sillén et al, ). Low‐dose ticagrelor has been recommended in clinical therapy because it yields similar antiplatelet efficacy and has fewer side reactions compared with standard‐dose ticagrelor (180 mg) (Lee, Kim, Choi, Lee, & Lee, ; Li et al, ; Storey et al, ).…”

Section: Introductionmentioning

confidence: 99%

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Validated liquid chromatography–tandem mass spectrometry method for quantification of ticagrelor and its active metabolite in human plasma

Ding

Yuan

et al. 2019

Biomedical Chromatography

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A rapid, simple and sensitive LC-MS/MS method was established and validated for simultaneous quantification of ticagrelor and its active metabolite AR-C124910XX in human plasma. After plasma samples were deproteinized with acetonitrile, the post-treatment samples were chromatographed on a Dikma C 18 column interfaced with a triple quadrupole tandem mass spectrometer. Electrospray negative ionization mode and multiple reaction monitoring were adopted to assay ticagrelor and AR-C124910XX. Acetonitrile and 5 mΜ ammonium acetate was used as the mobile phase with a gradient elution at a flow rate of 0.5 mL/min. The method was linear in the range of 0.781-800 ng/mL for both ticagrelor and AR-C124910XX with a correlation coefficient ≥0.994. The intra-and inter-day precisions were within 12.61% in terms of relative standard deviation and the accuracy was within ±7.88% in terms of relative error. The LC-MS/MS method was fully validated for its sensitivity, selectivity, stability, matrix effect and recovery. This convenient and specific LC-MS/MS method was successfully applied to the pharmacokinetic study of ticagrelor and AR-C124910XX in healthy volunteers after an oral dose of 90 mg ticagrelor.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Validated liquid chromatography–tandem mass spectrometry method for quantification of ticagrelor and its active metabolite in human plasma

Ding

Yuan

et al. 2019

Biomedical Chromatography

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“…Detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring and with a positive electrospray ionization interface. The method was validated and successfully applied to determine TCG and ARC124910XX simultaneously in human plasma and proved to be suitable for TCG pharmacokinetic study (Peng et al, ).…”

Section: Methodsmentioning

confidence: 99%

Analytical methodologies for the determination of ticagrelor

Kelemen

Hancu

Papp

2019

Biomedical Chromatography

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Ticagrelor is an orally administered platelet aggregation inhibitor with a cyclopentyl‐triazolopyrimidine structure; it is a selective reversible P2Y12 receptor antagonist, which prevents P2Y12‐mediated and ADP‐mediated platelet activation and aggregation. It is used to reduce the rate of cardiovascular death, myocardial infarction and stroke in patients with acute coronary syndrome or history of myocardial infarction. Several analytical methods have been published for the determination of ticagrelor in pharmaceuticals and biological materials by spectrophotometry, high‐performance liquid chromatography with ultraviolet detection and liquid chromatography coupled with tandem mass spectrometry. The purpose of the current review is to provide a systematic survey of the analytical techniques used for the determination of ticagrelor since its introduction in therapy until today.

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“…The most abundant compound was ticagrelor-TP478 (155±43 ng/g dw; CL3), also known as AR-C124910XX or deshydroxyethoxyticagrelor. [48][49][50][51][52] This substance is the main metabolite of ticagrelor, a stroke prevention medication, and has to the best of our knowledge not been reported in sewage sludge or the environment before. 53 Ticagrelor, by comparison, occurred at ten-fold lower concentrations (13.2±3.8 ng/g dw; CL1), similar to that of a second ticagrelor TP, (TP536; 22.5±6 ng/g dw; CL3).…”

Section: Fluoropharmaceuticals Their Transformation Products and A Fl...mentioning

confidence: 99%

Pharmaceuticals account for a significant proportion of the extractable organic fluorine in municipal wastewater treatment plant sludge

Spaan

Seilitz

Plassmann

et al. 2022

Preprint

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Fluorine mass balance studies have shown that monomeric per- and polyfluoroalkyl substances (PFAS) with perfluoroalkyl chain lengths of ~5-14 carbon atoms (i.e., “conventional” PFAS) account for a fraction (~2%) of the extractable organic fluorine (EOF) in municipal wastewater treatment plant (WWTP) sludge. The identity of the remaining EOF has thus far been unclear, but may be partly attributable to fluorine-containing pharmaceuticals and pesticides used throughout society. To test this hypothesis, we applied high resolution mass spectrometry-based suspect screening to samples of municipal WWTP sludge which had been previously subjected to a fluorine mass balance. Sixteen pharmaceutical substances (including transformation products [TPs]), one pesticide, and thirteen conventional PFAS were confirmed at confidence levels 1-4, with concentrations ranging from 0.07-155 ng/g dw. Notably, eight pharmaceutical substances did not meet the OECD definition of PFAS. When converted to fluorine equivalents, the newly detected organofluorine substances increased the percentage of known EOF from ~2% to ~27%, of which ~22% was attributed to pharmaceutical- and pesticide substances, with the greatest contributions from a ticagrelor TP (4.0%), ezetimibe (3.9%), and bicalutamide (3.5%). These data highlight the importance of considering both unconventional- and non-PFAS organofluorine substances in addition to conventional PFAS when closing the organofluorine mass balance in WWTP sludge.

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An HPLC-MS/MS Method for the Quantitative Determination of Ticagrelor and its Active Metabolite AR-C124910XX in Human Plasma and its Application to a Clinical Study

Cited by 8 publications

References 0 publications

Validated liquid chromatography–tandem mass spectrometry method for quantification of ticagrelor and its active metabolite in human plasma

Validated liquid chromatography–tandem mass spectrometry method for quantification of ticagrelor and its active metabolite in human plasma

Analytical methodologies for the determination of ticagrelor

Pharmaceuticals account for a significant proportion of the extractable organic fluorine in municipal wastewater treatment plant sludge

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