Description: Quetiapine sulfoxide dihydrochloride (Quetiapine S-oxide 2HCl) is a major metabolite of Quetiapinem, which is a 2nd-generation antipsychotic acting as a 5-HT receptor agonist and a dopamine receptor antagonist.

Physicochemical Properties

Molecular Formula	C21H27CL2N3O3S
Molecular Weight	472.428382158279
Exact Mass	471.115
CAS #	329218-11-3
Related CAS #	Quetiapine;111974-69-7;Quetiapine hemifumarate;111974-72-2;Quetiapine sulfoxide;329216-63-9;Quetiapine sulfoxide hydrochloride;2448341-72-6
PubChem CID	45358163
Appearance	White to yellow solid powder
LogP	3.652
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	7
Rotatable Bond Count	6
Heavy Atom Count	30
Complexity	515
Defined Atom Stereocenter Count	0
InChi Key	MPRQQJUQOLNAFP-UHFFFAOYSA-N
InChi Code	InChI=1S/C21H25N3O3S.2ClH/c25-14-16-27-15-13-23-9-11-24(12-10-23)21-17-5-1-3-7-19(17)28(26)20-8-4-2-6-18(20)22-21;;/h1-8,25H,9-16H2;2*1H
Chemical Name	2-[2-[4-(11-oxobenzo[b][1,4]benzothiazepin-6-yl)piperazin-1-yl]ethoxy]ethanol;dihydrochloride
Synonyms	329218-11-3; Quetiapine sulfoxide (dihydrochloride); Quetiapine Sulfoxide Dihydrochloride; Ethanol, 2-[2-[4-(5-oxidodibenzo[b,f][1,4]thiazepin-11-yl)-1-piperazinyl]ethoxy]- ,dihydrochloride; Quetiapine S-oxide dihydrochloride; 2-[2-[4-(11-oxobenzo[b][1,4]benzothiazepin-6-yl)piperazin-1-yl]ethoxy]ethanol;dihydrochloride; ETHANOL,2-[2-[4-(5-OXIDODIBENZO[B,F][1,4]THIAZEPIN-11-YL)-1-PIPERAZINYL]ETHOXY]-,DIHYDROCHLORIDE;
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, avoid exposure to moisture.
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

Targets	Major metabolite of Quetiapine
ln Vivo	The estimated Cmax value of quetiapine sulfoxide is 77.3 ± 32.4 ng/mL (mean ± SD). For quetiapine sulfoxide, the calculated AUClast value is 1,286±458 ng·h/mL. The metabolic rate for quetiapine sulfoxide falls with time, averaging 30% after 72 hours following dosage compared to an average of 119% within 2 hours [1].
References	[1]. Comparison of Capillary and Venous Drug Concentrations After Administration of a Single Dose of Risperidone, Paliperidone, Quetiapine, Olanzapine, or Aripiprazole. Clin Pharmacol Drug Dev. 2016 Nov;5(6):528-537. [2]. Quetiapine and its metabolite norquetiapine: translation from in vitro pharmacology to in vivo efficacy in rodent models. Br J Pharmacol. 2016 Jan;173(1):155-66.
Additional Infomation	Background and purpose: Quetiapine has a range of clinical activity distinct from other atypical antipsychotic drugs, demonstrating efficacy as monotherapy in bipolar depression, major depressive disorder and generalized anxiety disorder. The neuropharmacological mechanisms underlying this clinical profile are not completely understood; however, the major active metabolite, norquetiapine, has been shown to have a distinct in vitro pharmacological profile consistent with a broad therapeutic range and may contribute to the clinical profile of quetiapine. Experimental approach: We evaluated quetiapine and norquetiapine, using in vitro binding and functional assays of targets known to be associated with antidepressant and anxiolytic drug actions and compared these activities with a representative range of established antipsychotics and antidepressants. To determine how the in vitro pharmacological properties translate into in vivo activity, we used preclinical animal models with translational relevance to established antidepressant-like and anxiolytic-like drug action. Key results: Norquetiapine had equivalent activity to established antidepressants at the noradrenaline transporter (NET), while quetiapine was inactive. Norquetiapine was active in the mouse forced swimming and rat learned helplessness tests. In in vivo receptor occupancy studies, norquetiapine had significant occupancy at NET at behaviourally relevant doses. Both quetiapine and norquetiapine were agonists at 5-HT1A receptors, and the anxiolytic-like activity of norquetiapine in rat punished responding was blocked by the 5-HT1A antagonist, WAY100635. Conclusions and implications: Quetiapine and norquetiapine have multiple in vitro pharmacological actions, and results from preclinical studies suggest that activity at NET and 5-HT1A receptors contributes to the antidepressant and anxiolytic effects in patients treated with quetiapine. [1] Risperidone, paliperidone, quetiapine, olanzapine, and aripiprazole are antipsychotic drugs approved for treating various psychiatric disorders, including schizophrenia. The objective of this randomized, parallel-group, open-label study was to compare finger-stick-based capillary with corresponding venous whole-blood and plasma concentrations for these drugs after administration of a single dose to healthy volunteers. All whole-blood and plasma drug concentrations were measured with validated liquid chromatography-tandem mass spectrometry methods. Capillary and venous concentrations (both in plasma and whole blood) were in close agreement, although a time-dependent difference was observed, most obviously for olanzapine and paliperidone, with slightly higher capillary versus venous drug concentrations during the first hours after administering a single dose. The observed difference between capillary and venous plasma drug concentrations is expected not to be relevant in clinical practice, considering the wide window of therapeutic concentrations and the wide range of drug concentrations in the patient population for a given dose. Based on these results, finger-stick-based capillary drug concentrations have been shown to approximate venous drug concentrations.[2]

Solubility Data

Solubility (In Vitro)	H2O : ~250 mg/mL (~529.18 mM)
Solubility (In Vivo)	Solubility in Formulation 1: 50 mg/mL (105.84 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1167 mL	10.5836 mL	21.1672 mL
	5 mM	0.4233 mL	2.1167 mL	4.2334 mL
	10 mM	0.2117 mL	1.0584 mL	2.1167 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.