Methotrexate-d₃is intended for use as an internal standard for the quantification of MTX by GC- or LC-MS. MTX is similar in structure to folic acid and aminopterin . It acts by inhibiting the metabolism of folic acid and blocking key enzymes in the synthesis of purines and pyrimidines required for cell proliferation.^1,2MTX is known to induce adenosine release, which mediates many of its anti-inflammatory effects, including the reduction of proinflammatory cytokines.^2,3,4Formulations containing MTX have been used in the treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions.^5,6MTX formulations are considered the gold standard of disease-modifying antirheumatic drug (DMARD) therapy to treat both the immune-inflammatory and joint destructive processes of rheumatoid arthritis.⁷

1.Tian, H., and Cronstein, B.N.Understanding the mechanisms of action of methotrexate: Implications for the treatment of rheumatoid arthritisBull. NYU Hosp. Jt. Dis.65(3)168-173(2007) 2.Swierkot, J., and Szechinski, J.Methotrexate in rheumatoid arthritisPharmacol. Rep.58(4)473-492(2006) 3.Chan, E.S.L., and Cronstein, B.N.Molecular action of methotrexate in inflammatory diseasesArthritis Res.4(4)266-273(2002) 4.Wessels, J.A.M., Huizinga, T.W.J., and Guchelaar, H.J.Recent insights in the pharmacological actions of methotrexate in the treatment of rheumatoid arthritisRheumatology47249-255(2008) 5.Cutolo, M., Sulli, A., Pizzorni, C., et al.Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritisAnn. Rheum. Dis.60(8)729-735(2001) 6.Christin-Maitre, S., Bouchard, P., and Spitz, I.M.Medical termination of pregnancyN. Engl. J. Med.342(13)946-956(2000) 7.Smolen, J.S., and Steiner, G.Therapeutic strategies for rheumatoid arthritisNat. Rev. Drug Dis.2(6)473-488(2003)