Major metabolite of Quetiapine

喹硫平亚砜的估计 Cmax 值为 77.3 ± 32.4 ng/mL（平均值 ± SD）。对于喹硫平亚砜，计算出的 AUClast 值为 1,286±458 ng·h/mL。喹硫平亚砜的代谢率随着时间的推移而下降，用药后 72 小时后平均代谢率下降 30%，而 2 小时内平均代谢率下降 119% [1]。

Metabolism / Metabolites
Quetiapine Sulfoxide is a known human metabolite of quetiapine.

[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 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]

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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]

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

84.58

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

注意: 如下所列的是一些常用的体内动物实验溶解配方，主要用于溶解难溶或不溶于水的产品（水溶度<1 mg/mL）。 建议您先取少量样品进行尝试，如该配方可行，再根据实验需求增加样品量。

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注射用配方1: DMSO : Tween 80： Saline = 10 : 5 : 85 (如： 100 μL DMSO → 50 μL Tween 80 → 850 μL Saline)
*生理盐水/Saline的制备：将0.9g氯化钠/NaCl溶解在100 mL ddH ₂ O中，得到澄清溶液。
注射用配方 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL DMSO → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)
注射用配方 3: DMSO : Corn oil = 10 : 90 (如： 100 μL DMSO → 900 μL Corn oil)
示例: 以注射用配方 3 (DMSO : Corn oil = 10 : 90) 为例说明, 如果要配制 1 mL 2.5 mg/mL的工作液, 您可以取 100 μL 25 mg/mL 澄清的 DMSO 储备液，加到 900 μL Corn oil/玉米油中, 混合均匀。

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注射用配方 4: DMSO : 20% SBE-β-CD in Saline = 10 : 90 [如：100 μL DMSO → 900 μL (20% SBE-β-CD in Saline)]
*20% SBE-β-CD in Saline的制备（4°C，储存1周）：将2g SBE-β-CD (磺丁基-β-环糊精) 溶解于10mL生理盐水中，得到澄清溶液。
注射用配方 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (如： 500 μL 2-Hydroxypropyl-β-cyclodextrin (羟丙基环胡精)→ 500 μL Saline)
注射用配方 6: DMSO : PEG300 : Castor oil : Saline = 5 : 10 : 20 : 65 (如： 50 μL DMSO → 100 μL PEG300 → 200 μL Castor oil → 650 μL Saline)
注射用配方 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (如： 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
注射用配方 8: 溶解于Cremophor/Ethanol (50 : 50), 然后用生理盐水稀释。
注射用配方 9: EtOH : Corn oil = 10 : 90 (如： 100 μL EtOH → 900 μL Corn oil)
注射用配方 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (如： 100 μL EtOH → 400 μL PEG300 → 50 μL Tween 80 → 450 μL Saline)

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口服配方 1: 悬浮于0.5% CMC Na (羧甲基纤维素钠)
口服配方 2: 悬浮于0.5% Carboxymethyl cellulose (羧甲基纤维素)
示例: 以口服配方 1 (悬浮于 0.5% CMC Na)为例说明, 如果要配制 100 mL 2.5 mg/mL 的工作液, 您可以先取0.5g CMC Na并将其溶解于100mL ddH2O中，得到0.5%CMC-Na澄清溶液；然后将250 mg待测化合物加到100 mL前述 0.5%CMC Na溶液中，得到悬浮液。

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口服配方 3: 溶解于 PEG400 (聚乙二醇400)
口服配方 4: 悬浮于0.2% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 5: 溶解于0.25% Tween 80 and 0.5% Carboxymethyl cellulose (羧甲基纤维素)
口服配方 6: 做成粉末与食物混合

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注意: 以上为较为常见方法，仅供参考， InvivoChem并未独立验证这些配方的准确性。具体溶剂的选择首先应参照文献已报道溶解方法、配方或剂型，对于某些尚未有文献报道溶解方法的化合物，需通过前期实验来确定（建议先取少量样品进行尝试），包括产品的溶解情况、梯度设置、动物的耐受性等。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。