7-hydroxymethotrexate and Central-Nervous-System-Neoplasms

The plasma concentrations of methotrexate (MTX) and its major metabolite 7-hydroxy methotrexate (7-OH-MTX) are highly correlated with the toxicities in patients with high-dose MTX therapy. Routine monitoring of MTX and 7-OH-MTX plasma levels is useful for dose adjustment of rescue drugs and toxicity prevention. A UHPLC-MS/MS method for simultaneous determination of plasma MTX and 7-OH-MTX was developed, validated, and applied in 181 plasma samples. The ion transition was m/z 455.2 → 308.2 for MTX and m/z 471.2 → 324.1 for 7-OH-MTX. The flow rate was 0.4 mL/min with a run time of 2.6 min. The calibration range was 0.002-2 μM for MTX, and 0.01-10 μM for 7-OH-MTX. The intra-day and inter-day inaccuracy and imprecision were -5.50% to 10.93% and less than 9.20% for both analytes. The internal standard (MTX-D

Topics: Calibration; Central Nervous System Neoplasms; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Drug Monitoring; Folic Acid Antagonists; Humans; Kidney; Liver; Lymphoma, Non-Hodgkin; Male; Methotrexate; Sensitivity and Specificity; Tandem Mass Spectrometry