5-HT_1a Receptor ( pKi = 5.74 ); 5-HT_2A Receptor ( pKi = 7.54 ); 5-HT_2C Receptor ( pKi = 5.55 ); D2 Receptor ( pKi = 7.25 ); 5-HT_1A Receptor ( pKi = 4.77 ); D2 Receptor ( pKi = 6.33 )

Quetiapine (<100 μM; 24 hours) has no significant effect on cell viability [2]. Quetiapine (10 μM) inhibits NO release, while LPS (0.1-100 ng/mL) concentration modulates [2]. Cell viability assay [2] Cell line: N9 microglia Concentration: 0, 0.1, 1, 10, 50 and 100 μM Incubation time: 24 hours Results: No significant effect on cells. viability at various concentrations below 100 μM, where significant toxicity was observed. RT-PCR[2] Cell line: N9 microglia Concentration: 10 μM Incubation time: 24 hours Results: Significantly inhibited TNF-α synthesis.

Quetiapine (10 mg/kg/day; approved) can attenuate the recruitment and activation of astrocytes and promote myelin repair in a cuprizone (CPZ)-induced chronic demyelination model [2]. Animal model: C57BL/ 6 mice [2] Dosage: 10 mg/kg/day Administration method: Ingestion Results: Compared with the Veh group, the optical density of myelin basic protein (MBP) staining increased significantly.

In vitro binding studies [1]
Binding assays were performed using membranes prepared by standard methods from cells stably expressing cloned human targets. Displacement binding was performed using either scintillation proximity assay (SPA) (NET/HEK293F cells and 5‐HT2C/CHO‐K1 cells) or filtration (5‐HT transporter [SERT]/HEK293 cells, dopamine transporter [DAT]/CHO‐S cells, D2S/CHO‐K1 cells, 5‐HT1A/CHO cells and 5‐HT2A/CHO cells) using tritiated radioligands (MeNER, mesulergine, MADAM [2‐(2‐dimethylaminomethyl‐phenylsulphanyl)‐5‐methyl‐phenylamine], WIN 35428, raclopride, WAY100635 and MDL100907 respectively). The majority of IC50 values were calculated with fitting model 205 in XLfit. 5‐HT2A and 5‐HT2C IC50 values were calculated using prism software by GraphPad. Mean apparent inhibition constant (K i) values were calculated using the Cheng–Prusoff equation from data derived from at least three independent experiments. In vitro assessment of affinity at glutamate receptors was performed on preparations of rat cerebral cortex tissue. Binding at NMDA receptors was evaluated with [3H]‐CGP39653 [3H]‐TCP and [3H]‐MDL 105,519 binding at kainite receptors was evaluated with [3H]‐kainic acid and binding at AMPA receptors was evaluated with [3H]‐AMPA according to standard validated protocols under conditions defined by the contractor. Compounds were evaluated in singlicate across eight concentrations (0.01, 0.1, 0.3, 1, 3, 10, 30 and 100 μM).

Cell Line: N9 microglial cells
Concentration: 0, 0.1, 1, 10, 50, and 100 μM
Incubation Time: 24 hours
Result: Had no significant effect on cell viabilities at various concentrations under 100 μM, in which significant toxicity could be observed.

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In vitro functional studies [1]
Uptake inhibition assays were performed using HEK293F cells stably expressing human NET, SERT and DAT. Cryopreserved cells were re‐suspended at 60K per well, centrifuged at 110 g for 1 min and incubated at 37°C for 3 h. Uptake inhibition was measured using the neurotransmitter transporter dye by a method slightly modified from that reported by Jorgensen et al. 2008. The most significant alteration to the method is that fluorescence intensity was evaluated on an Envision reader. Data were analysed by calculating the % effect with respect to total (0.5% DMSO final) and background signals. D2S pA2 was measured by the ability of a compound to inhibit the response to 3 μM dopamine (~EC80), using a GTPγS filtration binding assay similar to the method previously described by Lazareno (1999; Hudzik et al., 2008). 5‐HT1A agonist activity (potency and maximal concentration [Emax]) was determined with a GTPγS SPA binding assay using membranes derived from CHO cells stably expressing recombinant human 5‐HT1A receptors. Assay conditions are based on those previously reported (Jerning et al., 2002), though modified to an SPA format. An efficacy of 100% was defined as the maximal response to 5‐HT. 5‐HT2A and 5‐HT2C antagonist activity was measured with a FLIPR‐based method, as previously reported (Porter et al., 1999) using cell lines expressing 5‐HT2A and 5‐HT2C receptors. MTT Assay [2]
Cell viability was evaluated by the MTT reduction assay as described previously (Niu et al., 2010). The cells were seeded in a 96-well plate for 24 h before being exposed to Quetiapine alone (10 μm) orQuetiapine with LPS (100 ng/ml) for 24 h. MTT solution (0.5 mg/ml) was then added to each well and the cells were incubated for 1 h at 37°C and in 5% CO2. Subsequently, the supernatant was removed and the formation of farmazan was solubilized with DMSO and measured at 540 nm with SpectraMax M2e spectrophotomete. Nitrite Production Assessment [2]
Accumulation of nitrite (NO2−) in the culture media, an indicator of NO synthase activity, was measured by Griess Reaction. Cells at density of 3 × 104 cells/well were plated onto 96-well microtiter plates. Quetiapine with or without LPS (100 ng/ml) were added to the culture medium of N9 microglial cells for 48 h. Fifty microliters of culture supernatants were mixed with 50 μl Griess reagents (Part I: 1% sulfanilamide; Part II: 0.1% naphthylethylene diamide dihydrochlride and 2% phosphoric acid) at room temperature at 540 nm using the microplate reader. Nitrite concentration was calculated with reference to a standard curve of sodium nitrite.

C57BL/6 mice
10 mg/kg/day
Ingested

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Once animals were trained to a stable baseline for three consecutive days, drug testing began. Norquetiapine (0.3, 1, 2, 5 and 10 mg·kg−1, n ≥ 6 per dose) was dissolved in saline and delivered s.c. at 1 mL·kg−1, 15 min before testing. Quetiapine (2.5, 5, 10 and 20 mg·kg−1, n ≥ 8 per dose) was formulated in distilled water plus lactic acid drops (pH > 2.5) to dissolution and delivered p.o. at 2 mL·kg−1, 60 min before testing. Diazepam in an Abbott's cocktail (10% ethanol, 40% propylene glycol and 50% water) stock solution of 5 mg·mL−1 was diluted to dosing volume (0.3, 1 and 3 mg·kg−1, n ≥ 3 per dose) with a 50% concentration of Abbott's cocktail and delivered 30 min before testing. In combination studies, WAY100635 was dissolved in saline and delivered at 0.1 mg·kg−1, s.c., alongside the test drug.[1]

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Elevated plus maze with rats from prenatally stressed dams [1]
The procedure used to evaluate elevated plus maze performance of rats from prenatally stressed dams is described in detail by Peters et al. (2011). In short, male Sprague–Dawley rats born in‐house to prenatally stressed dams were housed singly in an animal room with constant temperature and a 24 h light/dark cycle, on restricted food but with free access to water. On the test day, rats were placed in the centre of the maze facing an open arm, and behaviour was recorded for exactly 5 min. The % time spent in the open arms, the % entries into the open and closed arms and the total number of entries into the open and closed arms were recorded. The rats were dosed s.c. with either vehicle (saline), Quetiapine or norquetiapine (5 or 10 mg·kg−1 in saline and lactic acid to dissolve them, pH adjusted with sodium bicarbonate to pH > 5) 15 min before testing in the elevated plus maze. The effects of drug treatment in the elevated plus maze were assessed using a one‐way anova followed by Dunnett's multiple comparison. The effect of stress in the vehicle‐treated animals was assessed with a one‐tailed t‐test.

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C57BL/6 mice were randomly assigned to one of the following four groups: control (CTL), in which mice fed regular chow and drank distilled water for 12 weeks; CPZ, in which mice fed 0.2% CPZ for 12 weeks to induce a chronic demyelination (Matsushima and Morell, 2001); Veh, in which mice fed 0.2% CPZ for 12 weeks, then fed regular chow, and drank vehicle water for 2 weeks; Quetiapine, in which mice fed 0.2% CPZ for 12 weeks, and then fed regular chow, and drank Quetiapine-containing water for 2 weeks. [2]

Absorption, Distribution and Excretion
Quetiapine is rapidly and well absorbed after oral administration. Steady-state plasma concentrations are reached within 48 hours, and peak plasma concentrations are reached within 1.5 hours. The bioavailability of the tablets is 100%. In Han Chinese patients with schizophrenia, after oral administration of a 300 mg extended-release formulation, the steady-state peak plasma concentration (Cmax) was approximately 467 ng/mL, and the steady-state AUC was 5094 ng·h/mL. Food affects the absorption of quetiapine, increasing Cmax by 25% and AUC by 15%. After oral administration of radiolabeled quetiapine, less than 1% of the original drug is detected in the urine, indicating active metabolism of quetiapine. Approximately 73% of the dose is detected in urine, and approximately 20% is detected in feces. Quetiapine is distributed throughout the body. The apparent volume of distribution is approximately 10 ± 4 L/kg. In a clinical study, the fasting clearance of quetiapine in healthy volunteers was 101.04 ± 39.11 L/h. Lower doses of quetiapine may be required in elderly patients, as clearance may be reduced by up to 50%. Lower doses may also be required in patients with hepatic impairment. Oral absorption of quetiapine fumarate is rapid, reaching peak plasma concentrations within 1.5 hours. The bioavailability of tablets is 100% compared to solutions. Food has minimal effect on the bioavailability of quetiapine, increasing Cmax and AUC by 25% and 15%, respectively. Steady-state plasma concentrations are expected to be reached within two days after administration. Quetiapine is widely distributed throughout the body, with an apparent volume of distribution of 10 ± 4 L/kg. At therapeutic concentrations, its plasma protein binding is 83%. The oral clearance of quetiapine in patients with hepatic impairment (n=8) was, on average, 30% lower than in healthy subjects. In 2 of the 8 patients with hepatic impairment, the AUC and Cmax values were 3 times higher than in healthy subjects. Because quetiapine is primarily metabolized by the liver, plasma drug concentrations are expected to be higher in individuals with impaired liver function…
For more complete data on absorption, distribution, and excretion of quetiapine (8 items), please visit the HSDB record page.

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Metabolism/Metabolites
Quetiapine is primarily metabolized by the liver. Sulfonation and oxidation are the main metabolic pathways for this drug. In vitro studies have shown that cytochrome P450 3A4 metabolizes quetiapine to an inactive sulfonyl metabolite and participates in the metabolism of its active metabolite, N-desalkylquetiapine. CYP2D6 also participates in the metabolism of quetiapine. One study identified three metabolites of N-desalkylquetiapine. Two metabolites were identified as N-desalkylquetiapine sulfoxide and 7-hydroxy-N-desalkylquetiapine. CYP2D6 has been shown to be responsible for the metabolism of quetiapine to the pharmacologically active metabolite, 7-hydroxy-N-desalkylquetiapine. Individual variability in CYP2D6 metabolism may affect the concentration of the active metabolite. Quetiapine is primarily metabolized in the liver to inactive metabolites via sulfonation and oxidation. In vitro studies have shown that cytochrome P-450 (CYP) 3A4 isoenzymes are involved in the metabolism of quetiapine to inactive sulfoxide metabolites, which are the major metabolites. Based on in vitro studies, quetiapine and its nine metabolites appear unlikely to inhibit CYP isoenzymes 1A2, 3A4, 2C9, 2C19, or 2D6. Known metabolites of quetiapine include 7-hydroxyquetiapine and quetiapine sulfoxide. It is primarily metabolized in the liver. Its main metabolic pathway involves cytochrome P450 3A4 (CYP3A4)-mediated sulfonation and the oxidation of terminal alcohols to carboxylic acids. The major sulfoxide metabolite of quetiapine is inactive. Quetiapine also undergoes hydroxylation, O-dealkylation, N-dealkylation, and II-binding reactions of the dibenzothiazole ring. 7-Hydroxy and 7-hydroxy-N-dealkylated metabolites appear to be active, but at extremely low concentrations. Elimination pathway: Quetiapine is primarily eliminated via hepatic metabolism. Following a single oral dose of 14C-quetiapine, less than 1% of the administered dose is excreted unchanged, indicating rapid metabolism. Approximately 73% and 20% of the dose are recovered in urine and feces, respectively. Half-life: 6 hours. The mean terminal half-life of quetiapine is approximately 6-7 hours.

Toxicity Summary
Identification and Uses: Quetiapine fumarate is used for the symptomatic treatment of psychotic disorders. Placebo-controlled studies (primarily in hospitalized patients with schizophrenia) have demonstrated the efficacy of quetiapine for short-term treatment of schizophrenia. Quetiapine can be used alone or in combination with lithium or sodium valproate for the treatment of acute manic episodes associated with bipolar I disorder. Quetiapine is also used for the treatment of depressive episodes associated with bipolar disorder. Human Exposure and Toxicity: The most common adverse reactions occurring in patients receiving quetiapine for schizophrenia or bipolar disorder, at a rate ≥5%, included somnolence, sedation, fatigue, stupor, dizziness, dry mouth, constipation, elevated ALT, weight gain, dyspepsia, abdominal pain, orthostatic hypotension, and pharyngitis, occurring at twice the rate in the placebo group. Animal studies have observed an association between quetiapine and the development of cataracts. Lens changes have also been reported in some patients receiving long-term quetiapine treatment, but a causal relationship has not been established. In controlled clinical trials, 0.6% of patients treated with quetiapine experienced seizures. Compared to the placebo group, elderly patients with dementia-related psychosis receiving atypical antipsychotic treatment appeared to have a higher risk of death. Adults and children with major depressive disorder and other mental illnesses may experience exacerbations of depressive symptoms and/or suicidal ideation and behavior (suicidal tendencies) or abnormal behavioral changes, regardless of whether they are taking antidepressants. Neuroleptic malignant syndrome (NMS) is a potentially fatal syndrome requiring immediate discontinuation of the drug and intensive symptomatic treatment. NMS has been reported in patients taking antipsychotics, including quetiapine. Contact dermatitis, maculopapular rash, and photosensitivity have been reported sporadically in clinical trials. Allergic reactions and Stevens-Johnson syndrome have been reported in postmarketing surveillance. Quetiapine appears to be excreted in small amounts into human breast milk. The effects of quetiapine on childbirth are unclear. The safety and efficacy of quetiapine in children under 18 years of age with bipolar depression have not been established. Quetiapine overdose can cause central nervous system depression and sinus tachycardia. In cases of high-dose overdose, intubation and mechanical ventilation may be required to alleviate respiratory depression. Although QTc interval prolongation may occur, its clinical significance remains unclear, as it is likely due to overcorrection caused by tachycardia. Chromosomal aberration assays in cultured human lymphocytes did not reveal quetiapine's chromosome breakage potential. Animal studies: In a 2-year mouse carcinogenicity study, quetiapine resulted in a dose-dependent increase in thyroid pigment deposition at doses of 75–750 mg/kg. While the specific type of pigment could not be identified, it was found to co-localize with quetiapine in thyroid follicular epithelial cells. The functional impact of this finding and its relevance to human risk are unclear. In dogs treated with quetiapine for 6 or 12 months (not 1 month), focal triangular cataracts appeared at the posterior suture junction of the lens at a dose of 100 mg/kg. This finding may be related to quetiapine's inhibition of cholesterol biosynthesis. In repeated-dose studies in dogs and monkeys, quetiapine resulted in a dose-dependent decrease in plasma cholesterol levels; however, in individual dogs, no correlation was found between plasma cholesterol levels and cataract development. The presence of Δ-8-cholesterol in plasma is consistent with the inhibition of the later stages of cholesterol biosynthesis in these species. A 25% reduction in extralentinal cortical cholesterol levels was also observed in a specific study of female dogs treated with quetiapine. Teratogenicity of quetiapine was investigated in rats and rabbits during organogenesis. No teratogenic effects were detected in rats at doses ranging from 25 to 200 mg/kg and in rabbits at doses ranging from 25 to 100 mg/kg. However, evidence of embryo/fetal toxicity exists. Delayed ossification of bones was detected in rat fetuses at doses of 50 and 200 mg/kg and in rabbit fetuses at doses of 50 and 100 mg/kg. Fetal weight was decreased in rat fetuses at a dose of 200 mg/kg and in rabbit fetuses at a dose of 100 mg/kg. An increased incidence of mild soft tissue deformities (wrist/tarsal curvature) was observed in rabbit fetuses at a dose of 100 mg/kg. Maternal toxicity (i.e., reduced weight gain and/or death) was observed in the high-dose group in rat studies and in all dose groups in rabbit studies. No drug-related effects were observed at doses of 1, 10, and 20 mg/kg in a rat perinatal/postpartum reproductive study. However, in a preliminary perinatal/postpartum study, increased fetal and pup mortality and decreased mean litter weight were observed at a dose of 150 mg/kg. The mutagenicity of quetiapine was tested in six in vitro bacterial gene mutation assays and one in vitro mammalian gene mutation assay using Chinese hamster ovary cells. However, it is possible that not all tested strains were treated with sufficiently high concentrations of quetiapine. Under metabolically activated conditions, quetiapine did indeed result in a reproducible increase in the mutation rate of one Salmonella typhimurium test strain. No evidence of chromosome breakage was obtained in the rat micronucleus assay. As with other drugs used to treat schizophrenia, the mechanism of action of quetiapine is unclear. However, its therapeutic effect in schizophrenia is thought to be mediated by co-mediated dopamine D2 receptor and serotonin type 2 (5HT2) receptor antagonism. Although quetiapine is known to bind to other receptors with similar affinity, binding to both dopamine D2 and serotonin 5HT2 receptors is crucial for its treatment of schizophrenia. Interactions: Co-administration of quetiapine (250 mg) with phenytoin sodium (100 mg) increases the mean oral clearance of quetiapine by 5-fold. For patients with schizophrenia receiving quetiapine and phenytoin sodium or other liver enzyme inducers (e.g., carbamazepine, barbiturates, rifampin, glucocorticoids), an increased dose of quetiapine may be necessary to control symptoms. Caution should be exercised if phenytoin sodium is discontinued and replaced with a non-inducer (e.g., sodium valproate). Co-administration of quetiapine (150 mg) with sodium valproate (500 mg) increases the mean maximum plasma concentration of quetiapine at steady state by 17%, but does not affect its absorption or mean oral clearance.
Thioridazine (200 mg) increases the oral clearance of quetiapine (300 mg) by 65%.
Cymetidine (400 mg) taken multiple times daily decreases the mean oral clearance of quetiapine (150 mg) by 20%.
For more complete data on drug interactions of quetiapine (out of 10), please visit the HSDB record page.

[1]. 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.

[2]. Quetiapine Inhibits Microglial Activation by Neutralizing Abnormal STIM1-Mediated Intercellular Calcium Homeostasis and Promotes Myelin Repair in a Cuprizone-Induced Mouse Model of Demyelination. Front Cell Neurosci. 2015 Dec 21;9:492.

Therapeutic Uses
Quetiapine is also used to treat depressive episodes associated with bipolar disorder. Quetiapine can be used alone or in combination with lithium or sodium valproate to treat acute manic episodes associated with type I bipolar disorder. Placebo-controlled studies (primarily in hospitalized patients with schizophrenia) have demonstrated the efficacy of quetiapine for short-term treatment of schizophrenia, with study durations of up to 6 weeks. Quetiapine fumarate is used for symptomatic treatment of psychotic disorders (e.g., schizophrenia). Drug Warnings /Black Box Warning/ Warning: Increased mortality in patients with dementia-related psychosis; Suicidal ideation and behavior: Increased mortality in patients with dementia-related psychosis: The risk of death is increased in patients with dementia-related psychosis receiving antipsychotic medication. Quetiapine is not approved for the treatment of dementia-related psychosis. Suicidal ideation and behavior: Short-term studies have shown that antidepressants increase the risk of suicidal ideation and behavior in children, adolescents, and young adults. These studies did not show that antidepressant use in patients aged 24 and older increased the risk of suicidal ideation and behavior; antidepressant use in patients aged 65 and older reduced the risk. For patients of all ages starting antidepressant treatment, close monitoring for disease progression and the onset of suicidal ideation and behavior is essential. Inform family members and caregivers of the need for close monitoring of the patient's condition and communication with the prescribing physician. Quetiapine is not approved for use in children under ten years of age. The mortality risk in elderly patients with dementia-related psychosis receiving atypical antipsychotic treatment appears to be higher than in those receiving a placebo. An analysis of 17 placebo-controlled trials (mean duration 10 weeks) showed that the mortality rate in elderly patients receiving atypical antipsychotics (e.g., quetiapine, aripiprazole, olanzapine, risperidone) was approximately 1.6 to 1.7 times higher than in those receiving a placebo. In typical 10-week controlled trials, the mortality rate in the drug treatment group was approximately 4.5%, while the mortality rate in the placebo group was approximately 2.6%. Although the causes of death varied, most deaths appeared to be related to cardiovascular disease (e.g., heart failure, sudden death) or infectious diseases (e.g., pneumonia). The manufacturer states that quetiapine is not approved for the treatment of dementia-related psychosis. Short-term studies have shown that antidepressants increase the risk of suicidal ideation and behavior (suicidal tendency) in children and adolescents with major depressive disorder (MDD) and other mental illnesses. Anyone considering the use of quetiapine or other antidepressants in children or adolescents must weigh this risk against clinical need. Patients starting treatment should be closely monitored for worsening of their condition, suicidal tendency, or changes in unusual behavior. Family members and caregivers should be informed of the need for close monitoring and communication with the prescribing physician. Quetiapine is not approved for use in pediatric patients. A pooled analysis of short-term (4 to 16 weeks) placebo-controlled trials (24 trials involving more than 4,400 patients) of nine antidepressants (SSRIs and others) in children and adolescents with major depressive disorder (MDD), obsessive-compulsive disorder (OCD), or other mental illnesses showed that patients receiving antidepressant treatment had a higher risk of adverse events representing suicidal ideation or behavior (suicidal tendency) during the first few months of treatment. The average risk of such events in patients receiving antidepressant treatment is 4%, twice the 2% risk in the placebo group. For more complete data on drug warnings (of 31), please visit the HSDB record page. Pharmacodynamics: Quetiapine improves both positive and negative symptoms of schizophrenia and major depressive disorder by acting on multiple neurotransmitter receptors, such as serotonin and dopamine receptors. In bipolar disorder, it improves both depressive and manic symptoms. Precautions regarding suicidal ideation in young patients and use in older patients Quetiapine may cause suicidal ideation or behavior in children and adolescents and therefore should not be given to children under 10 years of age. If this medication is used in younger patients, suicidal ideation must be monitored. Furthermore, due to the increased mortality rate in older patients taking this medication, it is not indicated for the treatment of psychosis associated with dementia.

C21H25N3O2S

383.51

383.166

C, 65.77; H, 6.57; N, 10.96; O, 8.34; S, 8.36

111974-69-7

Quetiapine hemifumarate; 111974-72-2; Quetiapine sulfoxide dihydrochloride;329218-11-3; Quetiapine-d4 fumarate; 1287376-15-1; Quetiapine sulfoxide; 329216-63-9; 918505-61-0 (analog); Quetiapine; 111974-69-7; Quetiapine-d4 hemifumarate; 1217310-65-0; Quetiapine-d8 fumarate; 1185247-12-4; Quetiapine-d8 hemifumarate; Quetiapine hemifumarate-d8; 1435938-24-1

5002

Light yellow to yellow oil

1.3±0.1 g/cm3

556.5±60.0 °C at 760 mmHg

172 - 174ºC

290.4±32.9 °C

0.0±1.6 mmHg at 25°C

1.653

1.57

1

5

6

27

496

0

OCCOCCN(CC1)CCN1C2=NC3=CC=CC=C3SC4=C2C=CC=C4

URKOMYMAXPYINW-UHFFFAOYSA-N

InChI=1S/C21H25N3O2S/c25-14-16-26-15-13-23-9-11-24(12-10-23)21-17-5-1-3-7-19(17)27-20-8-4-2-6-18(20)22-21/h1-8,25H,9-16H2

2-[2-(4-benzo[b][1,4]benzothiazepin-6-ylpiperazin-1-yl)ethoxy]ethanol

ICI 204636; ICI-204636; ICI 204,636; 111974-69-7; Seroquel; Quetiapine fumarate; Norsic; Co-Quetiapine; quetiapina; quetiapinum; ICI204636; Quetiapine; quetiapine fumarate; brand name: Seroquel

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)

DMSO: 77~100 mg/mL (200.8~260.8 mM)
Ethanol: ~100 mg/mL (~260.8 mM)
H2O: ~0.1 mg/mL (~0.3 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.52 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (6.52 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (6.52 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.

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