7-Hydroxymethotrexate
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MedKoo CAT#: 597169

CAS#: 5939-37-7

Description: 7-Hydroxymethotrexate is a phase I metabolite of MTX, which is converted by hepatic aldehyde oxidases. Elimination of 7-hydroxy MTX is associated with the multi-drug transporters Abcc2, Abcc3, and Abcg2 in transgenic mouse models. It and the parent compound rapidly accumulate when all three transporters are absent.2 Formulations containing methotrexate have been used in the treatment of cancer, autoimmune diseases, ectopic pregnancy, and for the induction of medical abortions. Various methods have been described to quantify 7-hydroxy MTX levels during cancer therapy to avoid toxicity.

Chemical Structure

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7-Hydroxymethotrexate
CAS# 5939-37-7
Instruction

Theoretical Analysis

MedKoo Cat#: 597169
Name: 7-Hydroxymethotrexate
CAS#: 5939-37-7
Chemical Formula: C20H22N8O6
Exact Mass: 470.17
Molecular Weight: 470.440
Elemental Analysis: C, 51.06; H, 4.71; N, 23.82; O, 20.40

Price and Availability

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1mg USD 350
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Synonym: 7-Hydroxymethotrexate; NSC 380963; NSC-380963; NSC380963; NSC 380962; NSC-380962; NSC380962;

IUPAC/Chemical Name: (4-(((2,4-diamino-7-oxo-1,7-dihydropteridin-6-yl)methyl)(methyl)amino)benzoyl)-L-glutamic acid

InChi Key: HODZDDDNGRLGSI-NSHDSACASA-N

InChi Code: InChI=1S/C20H22N8O6/c1-28(8-12-18(32)26-16-14(23-12)15(21)25-20(22)27-16)10-4-2-9(3-5-10)17(31)24-11(19(33)34)6-7-13(29)30/h2-5,11H,6-8H2,1H3,(H,24,31)(H,29,30)(H,33,34)(H5,21,22,25,26,27,32)/t11-/m0/s1

SMILES Code: O=C(O)CC[C@@H](C(O)=O)NC(C1=CC=C(N(CC2=NC3=C(N)N=C(N)NC3=NC2=O)C)C=C1)=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >3 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.03.00

More Info:

Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 470.44 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
In vivo protocol:

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1: Silva MF, Ribeiro C, Gonçalves VMF, Tiritan ME, Lima Á. Liquid chromatographic methods for the therapeutic drug monitoring of methotrexate as clinical decision support for personalized medicine: A brief review. Biomed Chromatogr. 2018 May;32(5):e4159. doi: 10.1002/bmc.4159. Epub 2018 Jan 12. Review. PubMed PMID: 29226354.

2: Fabresse N, Devictor B, Pissier C, Chambost H, Lacarelle B, Michel G, Solas C. Plasma 7-Hydroxymethotrexate Levels Versus Methotrexate to Predict Delayed Elimination in Children Receiving High-Dose Methotrexate. Ther Drug Monit. 2018 Feb;40(1):76-83. doi: 10.1097/FTD.0000000000000445. PubMed PMID: 29120974.

3: Białk-Bielińska A, Mulkiewicz E, Stokowski M, Stolte S, Stepnowski P. Acute aquatic toxicity assessment of six anti-cancer drugs and one metabolite using biotest battery - Biological effects and stability under test conditions. Chemosphere. 2017 Dec;189:689-698. doi: 10.1016/j.chemosphere.2017.08.174. Epub 2017 Sep 21. PubMed PMID: 28968575.

4: Patel H, Giri P, Ghoghari A, Delvadia P, Syed M, Srinivas NR. Review of the bioanalytical methods for the determination of methotrexate and its metabolites in in vitro, preclinical and clinical studies: Case studies and perspectives. Biomed Chromatogr. 2017 Jan;31(1). doi: 10.1002/bmc.3849. Epub 2016 Oct 17. Review. PubMed PMID: 27623319.

5: Roberts MS, Selvo NS, Roberts JK, Daryani VM, Owens TS, Harstead KE, Gajjar A, Stewart CF. Determination of Methotrexate, 7-Hydroxymethotrexate, and 2,4-Diamino-N(10)-methylpteroic Acid by LC-MS/MS in Plasma and Cerebrospinal Fluid and Application in a Pharmacokinetic Analysis of High-Dose Methotrexate. J Liq Chromatogr Relat Technol. 2016;39(16):745-751. doi: 10.1080/10826076.2016.1243558. Epub 2016 Oct 10. PubMed PMID: 28824272; PubMed Central PMCID: PMC5560609.

6: Schofield RC, Ramanathan LV, Murata K, Fleisher M, Pessin MS, Carlow DC. Development of an Assay for Methotrexate and Its Metabolites 7-Hydroxy Methotrexate and DAMPA in Serum by LC-MS/MS. Methods Mol Biol. 2016;1383:213-22. doi: 10.1007/978-1-4939-3252-8_23. PubMed PMID: 26660190.

7: Schofield RC, Ramanathan LV, Murata K, Grace M, Fleisher M, Pessin MS, Carlow DC. Development and validation of a turbulent flow chromatography and tandem mass spectrometry method for the quantitation of methotrexate and its metabolites 7-hydroxy methotrexate and DAMPA in serum. J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Oct 1;1002:169-75. doi: 10.1016/j.jchromb.2015.08.025. Epub 2015 Aug 22. PubMed PMID: 26322588; PubMed Central PMCID: PMC4982141.

8: Řiháček M, Pilatova K, Štěrba J, Pilný R, Valík D. [New Indings in Methotrexate Pharmacology -  Diagnostic Possibilities and Impact on Clinical Care]. Klin Onkol. 2015;28(3):163-70. Review. Czech. PubMed PMID: 26062617.

9: Bluett J, Riba-Garcia I, Hollywood K, Verstappen SM, Barton A, Unwin RD. A HPLC-SRM-MS based method for the detection and quantification of methotrexate in urine at doses used in clinical practice for patients with rheumatological disease: a potential measure of adherence. Analyst. 2015 Mar 21;140(6):1981-7. doi: 10.1039/c4an02321h. PubMed PMID: 25671614.

10: Kozaki T, Tagashira M, Yamanishi K, Ellis B, Kayanoki T, Ooishi R, Sugiyama K, Matsuda S, Tsuruta K, Kohira T, Tsurui K. Evaluation of drug-drug interaction between the novel cPLA2 inhibitor AK106-001616 and methotrexate in rheumatoid arthritis patients. Xenobiotica. 2015;45(7):615-24. doi: 10.3109/00498254.2014.1000430. Epub 2015 Jan 12. PubMed PMID: 25579091.

11: Csordas K, Hegyi M, Eipel OT, Muller J, Erdelyi DJ, Kovacs GT. Comparison of pharmacokinetics and toxicity after high-dose methotrexate treatments in children with acute lymphoblastic leukemia. Anticancer Drugs. 2013 Feb;24(2):189-97. doi: 10.1097/CAD.0b013e32835b8662. PubMed PMID: 23187460.

12: Schmitt C, Kuhn B, Zhang X, Kivitz A, Grange S. Tocilizumab has no clinically relevant effects on methotrexate pharmacokinetics in patients with rheumatoid arthritis. Int J Clin Pharmacol Ther. 2012 Mar;50(3):218-23. PubMed PMID: 22373834.

13: Csordás K, Eipel O, Hegyi M, Csóka M, Pap E, Kovács G. [Pharmacokinetic analysis of high-dose methotrexate treatments in children with hematologic malignancies]. Orv Hetil. 2011 Oct 2;152(40):1609-17. doi: 10.1556/OH.2011.29143. Hungarian. PubMed PMID: 21945870.

14: Klapkova E, Kukacka J, Kotaska K, Suchanska I, Urinovska R, Prusa R. The influence of 7-OH methotrexate metabolite on clinical relevance of methotrexate determination. Clin Lab. 2011;57(7-8):599-606. PubMed PMID: 21888024.

15: Wang Z, Zhou Q, Kruh GD, Gallo JM. Dose-dependent disposition of methotrexate in Abcc2 and Abcc3 gene knockout murine models. Drug Metab Dispos. 2011 Nov;39(11):2155-61. doi: 10.1124/dmd.111.041228. Epub 2011 Aug 12. PubMed PMID: 21841039; PubMed Central PMCID: PMC3198900.

16: Meesters RJ, den Boer E, Mathot RA, de Jonge R, van Klaveren RJ, Lindemans J, Luider TM. Ultrafast selective quantification of methotrexate in human plasma by high-throughput MALDI-isotope dilution mass spectrometry. Bioanalysis. 2011 Jun;3(12):1369-78. doi: 10.4155/bio.11.113. PubMed PMID: 21679031.

17: Vlaming ML, van Esch A, van de Steeg E, Pala Z, Wagenaar E, van Tellingen O, Schinkel AH. Impact of abcc2 [multidrug resistance-associated protein (MRP) 2], abcc3 (MRP3), and abcg2 (breast cancer resistance protein) on the oral pharmacokinetics of methotrexate and its main metabolite 7-hydroxymethotrexate. Drug Metab Dispos. 2011 Aug;39(8):1338-44. doi: 10.1124/dmd.111.038794. Epub 2011 May 12. PubMed PMID: 21566011.

18: Uchiyama M, Matsumoto T, Matsumoto T, Jimi S, Takamatsu Y, Tamura K, Hara S. Simple and sensitive HPLC method for the fluorometric determination of methotrexate and its major metabolites in human plasma by post-column photochemical reaction. Biomed Chromatogr. 2012 Jan;26(1):76-80. doi: 10.1002/bmc.1628. Epub 2011 Mar 25. PubMed PMID: 21437923.

19: Chládková J, Hak J, Martínková J, Chládek J. High-dose methotrexate in children with acute lymphoblastic leukemia: 7-hydroxymethotrexate systemic exposure and urinary concentrations at the steady state correlate well with those of methotrexate. Arzneimittelforschung. 2010;60(12):769-75. doi: 10.1055/s-0031-1296353. PubMed PMID: 21265469.

20: Baluom M, Samara E, Grossbard EB, Lau DT. Fostamatinib, a Syk-kinase inhibitor, does not affect methotrexate pharmacokinetics in patients with rheumatoid arthritis. J Clin Pharmacol. 2011 Sep;51(9):1310-8. doi: 10.1177/0091270010381496. Epub 2011 Jan 5. PubMed PMID: 21209239.