Physicochemical Properties
| Molecular Formula | C9H14CLNO3 |
| Molecular Weight | 219.665 |
| Exact Mass | 219.066 |
| Elemental Analysis | C, 49.21; H, 6.42; Cl, 16.14; N, 6.38; O, 21.85 |
| CAS # | 1011-74-1 |
| Related CAS # | Normetanephrine-d3 hydrochloride;1085333-97-6 |
| PubChem CID | 102542 |
| Appearance | White to light yellow solid powder |
| Boiling Point | 393.8ºC at 760mmHg |
| Melting Point | 204ºC (dec.)(lit.) |
| Flash Point | 192ºC |
| Vapour Pressure | 1.13E-07mmHg at 25°C |
| LogP | 1.895 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 3 |
| Heavy Atom Count | 14 |
| Complexity | 154 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | VKFPRGQZWKTEON-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C9H13NO3.ClH/c1-13-9-4-6(8(12)5-10)2-3-7(9)11;/h2-4,8,11-12H,5,10H2,1H3;1H |
| Chemical Name | 4-(2-amino-1-hydroxyethyl)-2-methoxyphenol hydrochloride |
| Synonyms | Normetanephrine HCl; Normetanephrine hydrochloride; DL-α-(Aminomethyl)-4-hydroxy-3-methoxybenzenemethanol hydrochloride; |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | One extra methyl group distinguishes norepinephrine hydrochloride as a norepinephrine metabolite [2]. |
| References | 1: Marušić R, Dragila Ž, Levaković A, Lekić I, Mihaljević D, Debeljak Ž, Bačun T. The most common indications for measuring metanephrine and normetanephrine in plasma - a rational approach. Med Glas (Zenica). 2023 Aug 1;20(2). doi: 10.17392/1588-23. Epub ahead of print. PMID: 37300464. 2: Prego MT, Dias MJ, Ferreira RL, Gonçalves S, Dias Domingues T, Junius G, Van den Steen E, Galac S, Leal RO. Plasma and urinary metanephrine and normetanephrine concentrations using liquid chromatography with tandem mass spectrometry in healthy cats and in a cat with pheochromocytoma. J Vet Intern Med. 2023 May-Jun;37(3):910-914. doi: 10.1111/jvim.16648. Epub 2023 Apr 13. PMID: 37057306; PMCID: PMC10229322. 3: Yu Y, Chen C, Han W, Zhang Y, Zhang Z, Yang Y. Metanephrine and normetanephrine associated with subclinical myocardial injuries in pheochromocytoma and paraganglioma. Front Oncol. 2022 Sep 27;12:1024342. doi: 10.3389/fonc.2022.1024342. PMID: 36237312; PMCID: PMC9552905. 4: Deng Y, Liu Q, Liu Z, Zhao H, Zhou W, Zhang C. Commutability Assessment of Processed Human Plasma Samples for Normetanephrine and Metanephrine Measurements Based on the Candidate Reference Measurement Procedure. Ann Lab Med. 2022 Sep 1;42(5):575-584. doi: 10.3343/alm.2022.42.5.575. PMID: 35470275; PMCID: PMC9057823. 5: Remde H, Pamporaki C, Quinkler M, Nölting S, Prejbisz A, Timmers HJLM, Masjkur J, Fuss CT, Fassnacht M, Eisenhofer G, Deutschbein T. Improved Diagnostic Accuracy of Clonidine Suppression Testing Using an Age-Related Cutoff for Plasma Normetanephrine. Hypertension. 2022 Jun;79(6):1257-1264. doi: 10.1161/HYPERTENSIONAHA.122.19019. Epub 2022 Apr 5. PMID: 35378989. 6: Liu W, Zhang J, Yang Y, Jin Y, Li Z, You L, Luo J, Su X. Application of Metanephrine and Normetanephrine in Evaluating the Selectivity of Adrenal Vein Sampling. Horm Metab Res. 2022 Mar;54(3):162-167. doi: 10.1055/a-1756-4937. Epub 2022 Mar 11. PMID: 35276741. 7: Höglund K, Palmqvist H, Ringmark S, Svensson A. Quantification of normetanephrine in canine urine using ELISA: evaluation of factors affecting results. J Vet Diagn Invest. 2022 Jan;34(1):28-35. doi: 10.1177/10406387211052984. Epub 2021 Oct 26. PMID: 34697963; PMCID: PMC8689017. 8: Kline GA, Boyd J, Hyrcza M, Pacaud D, Pasieka JL, Dong Y, Sadrzadeh HSM, Leung AAC. Updated reference intervals for urine normetanephrine have no effect on test sensitivity but fewer false positives. Clin Biochem. 2022 Jan;99:17-19. doi: 10.1016/j.clinbiochem.2021.09.013. Epub 2021 Oct 6. PMID: 34626610. 9: Peitzsch M, Novos T, Kaden D, Kurlbaum M, van Herwaarden AE, Müller D, Adaway J, Grouzmann E, McWhinney B, Hoad K, Woollard G, Kema I, Boot C, Fassnacht M, Sweep F, Loh TP, Horvath AR, Eisenhofer G. Harmonization of LC-MS/MS Measurements of Plasma Free Normetanephrine, Metanephrine, and 3-Methoxytyramine. Clin Chem. 2021 Aug 5;67(8):1098-1112. doi: 10.1093/clinchem/hvab060. PMID: 33993248. 10: Mizuno K, Sakaue H, Kohsaka K, Takeda H, Hayashi N, Sato T. An increase in normetanephrine in hair follicles of acne lesions through the sympatho-adrenal medullary system in acne patients with anxiety. J Dermatol. 2021 Aug;48(8):1281-1285. doi: 10.1111/1346-8138.15935. Epub 2021 May 7. PMID: 33963607. 11: Kline GA, Boyd J, Leung AA, Tang A, Sadrzadeh HM. Moderate renal impairment does not preclude the accuracy of 24-hour urine normetanephrine measurements for suspected pheochromoctyoma. Clin Endocrinol (Oxf). 2020 Jun;92(6):518-524. doi: 10.1111/cen.14180. Epub 2020 Mar 18. PMID: 32133686. 12: Murabayashi M, Daimon M, Murakami H, Fujita T, Sato E, Tanabe J, Matsuhashi Y, Takayasu S, Yanagimachi M, Terui K, Kageyama K, Tokuda I, Sawada K, Ihara K. Association between higher urinary normetanephrine and insulin resistance in a Japanese population. PLoS One. 2020 Feb 13;15(2):e0228787. doi: 10.1371/journal.pone.0228787. PMID: 32053635; PMCID: PMC7018048. 13: Peitzsch M, Butch ER, Lovorn E, Mangelis A, Furman WL, Santana VM, Hero B, Berthold F, Shulkin BL, Huebner A, Eisenhofer G. Biochemical testing for neuroblastoma using plasma free 3-O-methyldopa, 3-methoxytyramine, and normetanephrine. Pediatr Blood Cancer. 2020 Feb;67(2):e28081. doi: 10.1002/pbc.28081. Epub 2019 Nov 14. PMID: 31724812. 14: Boyd J, Leung AA, Sadrzadeh HS, Pamporaki C, Pacak K, Deutschbein T, Fliedner S, Kline GA. A high rate of modestly elevated plasma normetanephrine in a population referred for suspected PPGL when measured in a seated position. Eur J Endocrinol. 2019 Sep;181(3):301-309. doi: 10.1530/EJE-19-0176. PMID: 31370003; PMCID: PMC7446766. 15: Peitzsch M, Mangelis A, Eisenhofer G, Huebner A. Age-specific pediatric reference intervals for plasma free normetanephrine, metanephrine, 3-methoxytyramine and 3-O-methyldopa: Particular importance for early infancy. Clin Chim Acta. 2019 Jul;494:100-105. doi: 10.1016/j.cca.2019.03.1620. Epub 2019 Mar 20. PMID: 30904545. 16: Godoy-Reyes TM, Costero AM, Gaviña P, Martínez-Máñez R, Sancenón F. Colorimetric detection of normetanephrine, a pheochromocytoma biomarker, using bifunctionalised gold nanoparticles. Anal Chim Acta. 2019 May 16;1056:146-152. doi: 10.1016/j.aca.2019.01.003. Epub 2019 Jan 8. PMID: 30797455. 17: Eisenhofer G, Peitzsch M, Kaden D, Langton K, Mangelis A, Pamporaki C, Masjkur J, Geroula A, Kurlbaum M, Deutschbein T, Beuschlein F, Prejbisz A, Bornstein SR, Lenders JWM. Reference intervals for LC-MS/MS measurements of plasma free, urinary free and urinary acid-hydrolyzed deconjugated normetanephrine, metanephrine and methoxytyramine. Clin Chim Acta. 2019 Mar;490:46-54. doi: 10.1016/j.cca.2018.12.019. Epub 2018 Dec 17. PMID: 30571948. 18: van den Ouweland JM, Mol M, Tax L, Beijers T, van Daal H. α-Methyldopa Interference in Urinary Normetanephrine Measurement by LC-MS/MS? J Appl Lab Med. 2016 Nov 1;1(3):321-324. doi: 10.1373/jalm.2016.020925. PMID: 33626849. 19: Bílek R, Zelinka T, Vlček P, Dušková J, Michalský D, Novák K, Bešťák J, Widimský J Jr. Deconjugated urinary metanephrine, normetanephrine and 3-methoxytyramine in laboratory diagnosis of pheochromocytoma and paraganglioma. Physiol Res. 2015;64(Suppl 2):S313-22. doi: 10.33549/physiolres.933109. PMID: 26680494. 20: Gabler J, Wang S. Quantification of Metanephrine and Normetanephrine in Urine Using Liquid Chromatography-Tandem Mass Spectrometry. Methods Mol Biol. 2016;1378:149-57. doi: 10.1007/978-1-4939-3182-8_17. PMID: 26602127. |
Solubility Data
| Solubility (In Vitro) |
H2O : ~100 mg/mL (~455.23 mM) DMSO : ~20.83 mg/mL (~94.82 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (9.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (9.47 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (9.47 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.5523 mL | 22.7614 mL | 45.5228 mL | |
| 5 mM | 0.9105 mL | 4.5523 mL | 9.1046 mL | |
| 10 mM | 0.4552 mL | 2.2761 mL | 4.5523 mL |