甲氨蝶呤
化学
硫嘌呤甲基转移酶
治疗药物监测
反叶绿体
药理学
淋巴细胞白血病
药品
内科学
白血病
抗代谢物
医学
炎症性肠病
疾病
作者
Rihwa Choi,Mi Ryung Chun,Ji Sook Park,Hojeong Won,Seonwoo Kim,Ji Won Lee,Hee Young Ju,Hee Won Cho,Hee Young Ju,Hong Hoe Koo,Eun Sang Yi,Soo‐Youn Lee
标识
DOI:10.1016/j.jpba.2021.114124
摘要
We developed and validated a quantification method for methotrexate (MTX) polyglutamates (MTX-PGs, MTX-PG1 to MTX-PG5) by liquid chromatography-tandem mass spectrometry using stable isotope-labeled internal standards and applied to 196 clinical samples collected from pediatric acute lymphoblastic leukemia patients treated with MTX. MTX-PGs levels and their proportions (%) in sum of all MTX-PGs (MTXSum) were evaluated in relation to TPMT, NUDT15, and MTHFR genotypes. For the developed method, linearity ranges 1−500 nmol/L, bias for accuracy 0.3–13.5 %, coefficient of variation for within- and between-run imprecision of 3.2−9.5% and 1.5−12.0%, respectively. Recoveries achieved were 74.2–105.8 %. There was no significant carryover. The median level of the MTXSum for 196 clinical samples was 129.4 nmol/L (interquartile range 28.1−241.2). MTX dose and MTX-PGs were associated (P < 0.05) and among five MTX-PGs, MTX-PG3 was the predominant form (median 41.7 %). The MTX-PG3 level was significantly higher in patients with TPMT *1/*3C than in patients with wild type and MTX-PG3% was significantly higher and MTX-PG5% was significantly lower in NUDT15 intermediate metabolizers than normal or indeterminate phenotypes (P < 0.05). This validated MTX-PGs quantification method can facilitate a better understanding of MTX metabolism and therapeutic drug monitoring for MTX treatment.
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