title: Simultaneous Determination of Ticagrelor and Its Metabolites in Human Plasma and Urine Using Liquid Chromatography-Tandem Mass Spectrometry.
abstract: We have developed and validated a rapid, selective and sensitive method using high-performance liquid chromatography-tandem mass spectrometry (MS) for the quantification of ticagrelor and all of its as-yet-identified metabolites in human plasma and urine. For the analysis of ticagrelor, its metabolites and the internal standard (IS) plasma samples were processed by liquid-liquid extraction using ethyl acetate and urine was processed by protein precipitation. Separations were performed on an Ultimate XB-C18 column (2.1 mm × 150 mm, 3 μm), using aqueous ammonium acetate (0.025 mM)/acetonitrile (35 : 65, v:v) as the mobile phase. Ticagrelor and all 11 metabolites were eluted within 4.5 min. Quantification was performed using electrospray ionization, operating in negative ion mode. The ticagrelor and metabolite M8 (AR-C124910XX) responses were optimized at the m/z 521.2 → 361.2 and m/z 477.2 → 361.1 transitions, respectively. The assay was validated over the linear range of 0.5-2,000 ng/mL for ticagrelor and M8. The intra- and inter-assay precisions were ≤14.6% for ticagrelor and ≤14.7% for M8, respectively. The matrix effects of plasma and urine were in the range of 98.3-110.7% for ticagrelor and 102.1-112.3% for M8. The relative quantification of other metabolites was performed by assessing the ratio of metabolite to IS peaks. The newly developed method was successfully used in a pharmacokinetic study characterizing ticagrelor metabolism in human volunteers.
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China Medical Research Center of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, 106 Zhongshan Road, Weilun Bldg 1112, Guangzhou 510080, PR China.
authors.forename: Wanping
authors.initials: W
authors.lastname: Zhong
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, 106 Zhongshan Road, Weilun Bldg 1112, Guangzhou 510080, PR China.
authors.forename: Xipei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Tang
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, 106 Zhongshan Road, Weilun Bldg 1112, Guangzhou 510080, PR China.
authors.forename: Liping
authors.initials: L
authors.lastname: Mai
authors.affiliation: Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha 410008, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Chen
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, 106 Zhongshan Road, Weilun Bldg 1112, Guangzhou 510080, PR China.
authors.forename: Guodong
authors.initials: G
authors.lastname: He
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, 106 Zhongshan Road, Weilun Bldg 1112, Guangzhou 510080, PR China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Medical Research Center of Guangdong General Hospital, Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, 106 Zhongshan Road, Weilun Bldg 1112, Guangzhou 510080, PR China zhongsl@hotmail.com.
authors.forename: Shilong
authors.initials: S
authors.lastname: Zhong
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D002853:Chromatography, Liquid; D058921:Purinergic P2Y Receptor Antagonists / Q000097:blood* / Q000493:pharmacokinetics / Q000652:urine; D053719:Tandem Mass Spectrometry; D000077486:Ticagrelor
chemical_list: D058921:Purinergic P2Y Receptor Antagonists; D000077486:Ticagrelor; D000241:Adenosine