title: Comparison of 6-mercaptopurine with 6-thioguanine for the analysis of thiopurine S-methyltransferase activity in human erythrocyte by LC-MS/MS.
abstract: Thiopurines (TPDs) are first-line drugs in treating neuromyelitis optica spectrum disorders (NMOSD). Evaluation of thiopurine S-methyltransferase activity (TPMT), a major determinant of TPD toxicity, before TPD treatment using 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) as substrate was suggested. However, the equivalent of the two substrates in TPMT activity evaluation was unknown, and an alternative substrate was required in TPMT activity evaluation in patients who were already taking 6-MP or 6-TG. Before evaluating the agreement of 6-MP and 6-TG in TPMT activity measurement in patients with NMOSD, the affinity of the two substrates for the active center of TPMT should be established. A computer-based simulation indicated that 6-MP and 6-TG had similar affinities for the two active sites of TPMT. According to the guidelines, an LC-MS/MS method was developed and validated to evaluate the TPMT activity in human erythrocyte hemolysate using 6-MP or 6-TG as substrates via 1 h incubation at 37°C. The method was applied in 81 patients with NMOSD. Evaluated by Bland-Altman plot, 6-methylmercaptopurine and 6-methylthioguanine represented TPMT activities were in agreement with each other. Further studies are warranted to confirm the results.
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.|Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Shenghui
authors.initials: S
authors.lastname: Mei
authors.affiliation: Neuroinfection and Neuroimmunology Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.|China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Xindi
authors.initials: X
authors.lastname: Li
authors.affiliation: Neuroinfection and Neuroimmunology Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.|China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Gong
authors.affiliation: College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.|Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.|Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Leting
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Neuroinfection and Neuroimmunology Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.|China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Neuroinfection and Neuroimmunology Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.|China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Neuroinfection and Neuroimmunology Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.|China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Anna
authors.initials: A
authors.lastname: Zhou
authors.affiliation: Neuroinfection and Neuroimmunology Center, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.|China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Xinghu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.
authors.forename: Zhigang
authors.identifier: http://orcid.org/0000-0003-0281-2259
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D004912:Erythrocytes / Q000201:enzymology*; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D015122:Mercaptopurine / Q000737:chemistry / Q000378:metabolism*; D008780:Methyltransferases / Q000097:blood* / Q000378:metabolism*; D008875:Middle Aged; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013866:Thioguanine / Q000737:chemistry / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015122:Mercaptopurine; D008780:Methyltransferases; C022745:thiopurine methyltransferase; D013866:Thioguanine
keywords: LC-MS/MS; method comparison; method development and validation; neuromyelitis optica spectrum disorders; thiopurine S-methyltransferase activity