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].

[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]

C21H27CL2N3O3S

472.428382158279

471.115

329218-11-3

Quetiapine;111974-69-7;Quetiapine hemifumarate;111974-72-2;Quetiapine sulfoxide;329216-63-9;Quetiapine sulfoxide hydrochloride;2448341-72-6

45358163

White to yellow solid powder

3.652

3

7

6

30

515

0

MPRQQJUQOLNAFP-UHFFFAOYSA-N

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

2-[2-[4-(11-oxobenzo[b][1,4]benzothiazepin-6-yl)piperazin-1-yl]ethoxy]ethanol;dihydrochloride

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;

2934.99.9001

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.

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

H2O : ~250 mg/mL (~529.18 mM)

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.)