Simultaneous quantification of ticagrelor anits active metabolite, AR-C124910XX, in human plasma by liquid chromatography-tandem mass spectrometry: Applications in steady-state pharmacokinetics in patients

Soon Uk Chae, Kyoung Lok Min, Chae Bin Lee, Zhouchi Huang, Min Jung Chang, Soo Kyung Bae

Research output: Contribution to journalArticle

Abstract

A sensitive and simple liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of ticagrelor and its active metabolite, AR-C124910XX from 50 μL human plasma using tolbutamide as an internal standard as per regulatory guidelines. Analytes in plasma were extracted by simple protein precipitation using acetonitrile, followed by chromatographic separation with an Acclaim™ RSLC 120 C18 column (2.2 μm, 2.1 × 100 mm) and a gradient acetonitrile-water mobile phase containing 0.1% formic acid within 8 min. Mass spectrometric detection and quantitation were conducted by selected reaction-monitoring on a negative electrospray ionization mode with the following transitions: m/z 521.11 → 361.10, 477.03 → 361.10, and 269.00 → 169.60 for ticagrelor, AR-C124910XX, and tolbutamide, respectively. The lower limit of quantifications was 0.2 ng/mL with linear ranges of 0.2−2,500 ng/mL (r2 ≥ 0.9949) for both analytes. All validation data, including selectivity, cross-talk, precision, accuracy, matrix effect, recovery, dilution integrity, stability, and incurred sample reanalysis, were well within acceptable limits. This assay method was validated using K2-EDTA as the specific anticoagulant. Also, the anticoagulant effect was tested by lithium heparin, sodium heparin, and K3-EDTA. No relevant anticoagulant effect was observed. This validated method was effectively used in the determination of ticagrelor and its active metabolite, AR-C124910XX, in plasma samples from patients with myocardial infarction.

Original languageEnglish
Pages (from-to)98-106
Number of pages9
JournalTranslational and Clinical Pharmacology
Volume27
Issue number3
DOIs
Publication statusPublished - 2019 Jan 1

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Tandem Mass Spectrometry
Liquid Chromatography
Anticoagulants
Tolbutamide
formic acid
Pharmacokinetics
Edetic Acid
Heparin
Lithium
Myocardial Infarction
Guidelines
Water
Ticagrelor
AR C124910XX
Proteins
acetonitrile

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)

Cite this

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title = "Simultaneous quantification of ticagrelor anits active metabolite, AR-C124910XX, in human plasma by liquid chromatography-tandem mass spectrometry: Applications in steady-state pharmacokinetics in patients",
abstract = "A sensitive and simple liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of ticagrelor and its active metabolite, AR-C124910XX from 50 μL human plasma using tolbutamide as an internal standard as per regulatory guidelines. Analytes in plasma were extracted by simple protein precipitation using acetonitrile, followed by chromatographic separation with an Acclaim™ RSLC 120 C18 column (2.2 μm, 2.1 × 100 mm) and a gradient acetonitrile-water mobile phase containing 0.1{\%} formic acid within 8 min. Mass spectrometric detection and quantitation were conducted by selected reaction-monitoring on a negative electrospray ionization mode with the following transitions: m/z 521.11 → 361.10, 477.03 → 361.10, and 269.00 → 169.60 for ticagrelor, AR-C124910XX, and tolbutamide, respectively. The lower limit of quantifications was 0.2 ng/mL with linear ranges of 0.2−2,500 ng/mL (r2 ≥ 0.9949) for both analytes. All validation data, including selectivity, cross-talk, precision, accuracy, matrix effect, recovery, dilution integrity, stability, and incurred sample reanalysis, were well within acceptable limits. This assay method was validated using K2-EDTA as the specific anticoagulant. Also, the anticoagulant effect was tested by lithium heparin, sodium heparin, and K3-EDTA. No relevant anticoagulant effect was observed. This validated method was effectively used in the determination of ticagrelor and its active metabolite, AR-C124910XX, in plasma samples from patients with myocardial infarction.",
author = "Chae, {Soon Uk} and Min, {Kyoung Lok} and Lee, {Chae Bin} and Zhouchi Huang and Chang, {Min Jung} and Bae, {Soo Kyung}",
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Simultaneous quantification of ticagrelor anits active metabolite, AR-C124910XX, in human plasma by liquid chromatography-tandem mass spectrometry : Applications in steady-state pharmacokinetics in patients. / Chae, Soon Uk; Min, Kyoung Lok; Lee, Chae Bin; Huang, Zhouchi; Chang, Min Jung; Bae, Soo Kyung.

In: Translational and Clinical Pharmacology, Vol. 27, No. 3, 01.01.2019, p. 98-106.

Research output: Contribution to journalArticle

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T1 - Simultaneous quantification of ticagrelor anits active metabolite, AR-C124910XX, in human plasma by liquid chromatography-tandem mass spectrometry

T2 - Applications in steady-state pharmacokinetics in patients

AU - Chae, Soon Uk

AU - Min, Kyoung Lok

AU - Lee, Chae Bin

AU - Huang, Zhouchi

AU - Chang, Min Jung

AU - Bae, Soo Kyung

PY - 2019/1/1

Y1 - 2019/1/1

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AB - A sensitive and simple liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of ticagrelor and its active metabolite, AR-C124910XX from 50 μL human plasma using tolbutamide as an internal standard as per regulatory guidelines. Analytes in plasma were extracted by simple protein precipitation using acetonitrile, followed by chromatographic separation with an Acclaim™ RSLC 120 C18 column (2.2 μm, 2.1 × 100 mm) and a gradient acetonitrile-water mobile phase containing 0.1% formic acid within 8 min. Mass spectrometric detection and quantitation were conducted by selected reaction-monitoring on a negative electrospray ionization mode with the following transitions: m/z 521.11 → 361.10, 477.03 → 361.10, and 269.00 → 169.60 for ticagrelor, AR-C124910XX, and tolbutamide, respectively. The lower limit of quantifications was 0.2 ng/mL with linear ranges of 0.2−2,500 ng/mL (r2 ≥ 0.9949) for both analytes. All validation data, including selectivity, cross-talk, precision, accuracy, matrix effect, recovery, dilution integrity, stability, and incurred sample reanalysis, were well within acceptable limits. This assay method was validated using K2-EDTA as the specific anticoagulant. Also, the anticoagulant effect was tested by lithium heparin, sodium heparin, and K3-EDTA. No relevant anticoagulant effect was observed. This validated method was effectively used in the determination of ticagrelor and its active metabolite, AR-C124910XX, in plasma samples from patients with myocardial infarction.

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