Acetaminophen-d4 is the deuterated form of Acetaminophen. Acetaminophen (Paracetamol) is a selective cyclooxygenase-2 (COX-2) inhibitor (antagonist) with IC50 of 25.8 μM. Acetaminophen is a potent hepatic N-acetyltransferase 2 (NAT2) inhibitor. Acetaminophen is a extensively used antipyretic and analgesic.

Physicochemical Properties

Molecular Formula	C8H5D4NO2
Molecular Weight	155.19
Exact Mass	155.088
CAS #	64315-36-2
Related CAS #	Acetaminophen;103-90-2
PubChem CID	12205925
Appearance	White to off-white solid powder
Melting Point	169-171°C (dec.)
Flash Point	9℃
LogP	1.423
Hydrogen Bond Donor Count	2
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	1
Heavy Atom Count	11
Complexity	139
Defined Atom Stereocenter Count	0
SMILES	[2H]C1=C(C(=C(C(=C1NC(=O)C)[2H])[2H])O)[2H]
InChi Key	RZVAJINKPMORJF-QFFDRWTDSA-N
InChi Code	InChI=1S/C8H9NO2/c1-6(10)9-7-2-4-8(11)5-3-7/h2-5,11H,1H3,(H,9,10)/i2D,3D,4D,5D
Chemical Name	N-(2,3,5,6-tetradeuterio-4-hydroxyphenyl)acetamide
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
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

Drug compounds have included stable heavy isotopes of carbon, hydrogen, and other elements, mostly as quantitative tracers while the drugs were being developed. Because deuteration may have an effect on a drug's pharmacokinetics and metabolic properties, it is a cause for concern [1].

References

[1]. Impact of Deuterium Substitution on the Pharmacokinetics of Pharmaceuticals. Ann Pharmacother. 2019;53(2):211-216. [2]. Acetaminophen (paracetamol) is a selective cyclooxygenase-2 inhibitor in man. FASEB J, 2008. 22(2): p. 383-90. [3]. Lactobacillus fermentum Postbiotic-induced Autophagy as Potential Approach for Treatment ofAcetaminophen Hepatotoxicity. Front Microbiol. 2017 Apr 6;8:594. [4]. Hepatoprotective Effect of Citral on Acetaminophen-Induced Liver Toxicity in Mice. Evid Based Complement Alternat Med. 2017;2017:1796209. [5]. Acetaminophen is an inhibitor of hepatic N-acetyltransferase 2 in vitro and in vivo. Pharmacogenetics. 1998 Dec;8(6):553-9.

Solubility Data

Solubility (In Vitro)

DMSO : ≥ 100 mg/mL (644.37 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (16.11 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 25.0 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: ≥ 2.5 mg/mL (16.11 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 25.0 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: ≥ 2.5 mg/mL (16.11 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 25.0 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	6.4437 mL	32.2186 mL	64.4371 mL
	5 mM	1.2887 mL	6.4437 mL	12.8874 mL
	10 mM	0.6444 mL	3.2219 mL	6.4437 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.