Major metabolite of Quetiapine

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].

Metabolism / Metabolites
Quetiapine sulfoxides are known metabolites of quetiapine in the human body.

[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.

Background and Objectives: Quetiapine possesses a different range of clinical activity than other atypical antipsychotics, and its monotherapy is effective against bipolar depression, major depressive disorder, and generalized anxiety disorder. Although the neuropharmacological mechanisms underlying its clinical efficacy are not fully elucidated, its main active metabolite, norquetiapine, has been shown to possess unique in vitro pharmacological characteristics consistent with its broad therapeutic range and may contribute to the clinical efficacy of quetiapine. Methods: We used in vitro binding and functional analyses to evaluate the binding and function of quetiapine and norquetiapine to known targets of action of antidepressants and anxiolytics, and compared these activities with a range of representative marketed antipsychotics and antidepressants. To determine how in vitro pharmacological properties translate into in vivo activity, we used preclinical animal models with translational relevance to the effects of marketed antidepressant-like and anxiolytic-like drugs. Main Results: Norquetiapine exhibited activity at the norepinephrine transporter (NET) comparable to known antidepressants, while quetiapine itself showed no activity. Norquetiapine showed activity in both the forced swimming test in mice and the learned helplessness test in rats. In vivo receptor occupancy studies showed that norquetiapine had a significant occupancy of NET at behaviorally relevant doses. Both quetiapine and norquetiapine are 5-HT1A receptor agonists, and the anxiolytic-like activity of norquetiapine in the punishment response in rats can be blocked by the 5-HT1A receptor antagonist WAY100635. Conclusion and significance: Quetiapine and norquetiapine have a variety of in vitro pharmacological effects. Preclinical studies have shown that their activity on NET and 5-HT1A receptors helps quetiapine exert antidepressant and anxiolytic effects in patients. [1] Risperidone, paliperidone, quetiapine, olanzapine and aripiprazole are approved antipsychotic drugs for the treatment of a variety of mental disorders, including schizophrenia. This randomized, parallel-group, open-label study aimed to compare the concentrations of the above drugs in fingertip capillary blood, whole venous blood and plasma in healthy volunteers after a single dose of the above drugs. All whole blood and plasma drug concentrations were determined using a validated liquid chromatography-tandem mass spectrometry method. Drug concentrations in capillary and venous blood (including plasma and whole blood) were generally consistent, but time-dependent differences were observed, particularly with olanzapine and paliperidone, with capillary blood drug concentrations being slightly higher than venous blood drug concentrations in the first few hours after a single dose. Given the wide range of therapeutic concentrations and the broad range of drug concentrations in the patient population for a given dose, the observed differences between capillary and venous plasma drug concentrations are not expected to be significant in clinical practice. Based on these results, capillary drug concentrations from finger-prick blood have been shown to approximate venous drug concentrations. [2]

C21H25N3O3S

399.5065

399.161

C, 63.14; H, 6.31; N, 10.52; O, 12.01; S, 8.02

329216-63-9

Quetiapine;111974-69-7;Quetiapine hemifumarate;111974-72-2;Quetiapine sulfoxide dihydrochloride;329218-11-3;Quetiapine sulfoxide hydrochloride;2448341-72-6;Quetiapine Sulfoxide-d8;1330238-38-4

10431050

Typically exists as solid at room temperature

1.4±0.1 g/cm3

611.3±65.0 °C at 760 mmHg

-48ºC

323.5±34.3 °C

0.0±1.8 mmHg at 25°C

1.675

-0.51

1

7

6

28

515

0

OCCOCCN(CC1)CCN1C2=NC(C=CC=C3)=C3S(C4=C2C=CC=C4)=O

FXJNLPUSSHEDON-UHFFFAOYSA-N

InChI=1S/C21H25N3O3S/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-[2-[4-(11-oxobenzo[b][1,4]benzothiazepin-6-yl)piperazin-1-yl]ethoxy]ethanol

Quetiapine Sulfoxide; 329216-63-9; Quetiapine S-Oxide; Ethanol, 2-[2-[4-(5-oxidodibenzo[b,f][1,4]thiazepin-11-yl)-1-piperazinyl]ethoxy]-; 2-[2-[4-(11-oxobenzo[b][1,4]benzothiazepin-6-yl)piperazin-1-yl]ethoxy]ethanol; Quetiapine metabolite Quetiapine sulfoxide; 1CW92313VM; 2-(2-(4-(5-Oxidodibenzo(b,f)(1,4)thiazepin-11-yl)piperazin-1-yl)ethoxy)ethanol;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)