Objectives: The aim of the study was to explore the effect of total glucosides of paeony (TGP) and Tripterygium wilfordii polyglycosides (TWP) on erythrocyte methotrexate polyglutamates (MTXPGs), the metabolites of methotrexate (MTX).
Methods: An ultra-high-performance liquid chromatography (UPLC)-tandem mass spectrometry (MS/MS) method was developed to determine MTXPGs. The effects of MTXPGs were analysed using 24 male Sprague-Dawley rats that were randomly divided into the MTX alone, MTX-TGP combined, and MTX-TWP combined groups. Rats were administered MTX at a dose of 0.9 mg/kg once a week, TGP at 0.054 g/kg and TWP at 1.8 mg/kg three times a day. Venous blood (1.0 ml) was collected at weeks 2, 4, 6, 9, 12 and 15 and then analysed using the developed UPLC-MS/MS method.
Key Findings: Specificity, linear range, inter-and intra-day precision, recovery, matrix effect and stability of MTXPGs met the standard regulations. This method was successfully used for the detection of MTXPGs. After administration of MTX alone, erythrocyte MTXPGs increased and accumulated in a time- and dose-dependent manner. Compared to MTX alone, the combination with TGP significantly decreased the content of total MTXPGs and short-chain MTXPGs (Methotrexate [MTX/MTXPG1] and 4-amino-10-methylpteroyldiglutamic acid [MTXPG2], P < 0.05), but had no significant effect on long-chain MTXPGs (4-amino-10-methylpteroyltriglutamic acid [MTXPG3], P > 0.05) and very long-chain MTXPGs (4-amino-10-methylpteroyltetraglutamic acid [MTXPG4] and 4-amino-10-methylpteroylpentaglutamic acid [MTXPG5], P > 0.05) at week 15. The combination of MTX with TWP had no significant effect on the content of total MTXPGs, short-chain MTXPGs and long-chain MTXPGs (P > 0.05), but it significantly decreased the content of very long-chain MTXPGs (P < 0.05) at week 15.
Conclusions: The UPLC-MS/MS method was successfully used to determine MTXPGs in rat erythrocytes. TGP and TWP in combination with MTX affected the production of MTXPGs of different chain lengths in erythrocytes.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1093/jpp/rgab025 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Association of methotrexate polyglutamates concentration with methotrexate efficacy and safety in patients with rheumatoid arthritis treated with predefined dose: results from the MIRACLE trial.
Ann Rheum Dis
January 2025
Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. Electronic address:
Objectives: The usefulness of methotrexate-polyglutamates (MTX-PGs) concentration for management of rheumatoid arthritis has been debated. We aimed to clarify the association of MTX-PGs concentration with efficacy and safety in MTX-naïve patients initiating MTX in a prospective interventional clinical trial.
Methods: The MIRACLE trial enrolled 300 MTX-naïve patients.
Assessment of Erythrocytes Methotrexate Polyglutamate Three Levels in Psoriatic Patients Treated with Methotrexate Monotherapy and Their Association with Disease Response.
Indian J Clin Biochem
January 2025
Department of Dermatology, JIPMER, Puducherry, 06 India.
Unlabelled: Methotrexate is used to manage moderate to severe psoriasis and psoriatic arthritis. Methotrexate acts by inhibiting the enzymes involved in nucleotide synthesis. Methotrexate polyglutamates (MTXPGs) have a higher potency to inhibit Dihydrofolate reductase (DHFR), 5-aminoimidazole-4-carboxamide ribonucleotide transformylase (ATIC), and thymidylate synthase (TS), compared to naïve methotrexate.
View Article and Find Full Text PDFTherapeutic Drug Monitoring of Low Methotrexate Doses for Drug Exposure and Adherence Assessment-Pre-Analytical Variables, Bioanalytical Issues, and Current Clinical Applications.
Int J Mol Sci
December 2024
Department of Drug Chemistry, Pharmaceutical and Biomedical Analysis, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.
Methotrexate (MTX) is an antifolic agent used in the first line of anti-inflammatory disease treatment and some oncologic issues. The metabolism of MTX is rapid, and the MTX concentration in the blood is not significant 24 h after administration. Unlike this, methotrexate polyglutamates (MTXPGs) can be informative biomarkers of drug exposure.
View Article and Find Full Text PDFLong-term evaluation of rheumatoid arthritis activity with erythrocyte methotrexate-polyglutamate 3.
Fundam Clin Pharmacol
February 2025
CHU Saint-Étienne, Service de Rhumatologie, Mines Saint-Etienne, INSERM, SAINBIOSE U1059, Université Jean Monnet Saint-Étienne, Saint-Etienne, France.
Background: Methotrexate (MTX) is the first-line treatment for Rheumatoid Arthritis (RA), yet 30%-50% of RA patients develop resistance to MTX, which can manifest several years after treatment initiation.
Objective: This study investigates the relationship between erythrocyte methotrexate polyglutamates (MTX-PGs) subtype concentrations and clinical disease activity in RA patients undergoing long-term MTX treatment.
Methods: In this cross-sectional study, patients on a stable dose of subcutaneous MTX for several years were included.
Methotrexate polyglutamates.
Expert Rev Clin Pharmacol
November 2024
Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, P. R. China.
Introduction: Methotrexate polyglutamates (MTXPGs) are intracellular metabolites of methotrexate (MTX) that play a critical role in the drug's activity, influencing both its efficacy and toxicity. As the exact implications of MTXPGs in these processes remain a subject of debate, a comprehensive review of MTXPGs could provide valuable insights for clinicians and pharmacists, potentially minimizing adverse reactions and enhancing therapeutic outcomes.
Areas Covered: A comprehensive search of relevant literature was conducted in PubMed and Web of Science databases, including studies from their inception to April 2024.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!