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Simultaneous determination of plasma methotrexate and 7-hydroxy methotrexate by UHPLC–MS/MS in patients receiving high-dose methotrexate therapy
- Source :
- Journal of Pharmaceutical and Biomedical Analysis. 158:300-306
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- 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-D3) normalized recovery and matrix factor were consistent at four quality control levels. 14 h, 38 h, and 62 h after dosing, MTX and 7-OH-MTX plasma levels were significantly higher in patients with impaired renal function compared to those with normal renal function. 7-OH-MTX plasma levels were significantly higher in patients with impaired liver function compared to those with normal liver function.
- Subjects :
- Male
musculoskeletal diseases
Metabolite
Clinical Biochemistry
Pharmaceutical Science
Renal function
Pharmacology
Kidney
Sensitivity and Specificity
030226 pharmacology & pharmacy
01 natural sciences
Analytical Chemistry
Central Nervous System Neoplasms
Matrix (chemical analysis)
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Tandem Mass Spectrometry
immune system diseases
Drug Discovery
medicine
Humans
heterocyclic compounds
In patient
Dosing
skin and connective tissue diseases
Chromatography, High Pressure Liquid
Spectroscopy
Dose-Response Relationship, Drug
Chemistry
Lymphoma, Non-Hodgkin
010401 analytical chemistry
0104 chemical sciences
Methotrexate
Liver
Calibration
Toxicity
Folic Acid Antagonists
Liver function
Drug Monitoring
medicine.drug
Subjects
Details
- ISSN :
- 07317085
- Volume :
- 158
- Database :
- OpenAIRE
- Journal :
- Journal of Pharmaceutical and Biomedical Analysis
- Accession number :
- edsair.doi.dedup.....fd615317d893662e5728341a9a4c5344