Quinidine N-oxide
目录号 : GC44799
A quinidine metabolite
Cas No.:70116-00-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Quinidine N-oxide is a pharmacologically inactive quinidine metabolite. Quinidine, an antiarrhythmic agent, undergoes rapid first-pass metabolism by the cytochrome P450 isoforms CYP3A4, CYP2C9, and CYP2E1, with CYP3A4 being the most active enzyme in quinidine N-oxide formation.
| Cas No. | 70116-00-6 | SDF | |
| Canonical SMILES | O[C@@H](C1=CC=NC2=CC=C(OC)C=C12)[C@](C[C@H]3[C@@H](C=C)C4)([H])[N]4(CC3)=O | ||
| 分子式 | C20H24N2O3 | 分子量 | 340.4 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.9377 mL | 14.6886 mL | 29.3772 mL |
| 5 mM | 0.5875 mL | 2.9377 mL | 5.8754 mL |
| 10 mM | 0.2938 mL | 1.4689 mL | 2.9377 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Determination of quinidine, dihydroquinidine, (3S)-3-hydroxyquinidine and Quinidine N-oxide in plasma and urine by high-performance liquid chromatography
J Chromatogr B Biomed Appl 1994 Oct 3;660(1):103-10.PMID:7858702DOI:10.1016/0378-4347(94)00259-2.
A specific and sensitive method for the quantitation of quinidine, (3S)-3-hydroxyquinidine, Quinidine N-oxide, and dihydroquinidine in plasma and urine has been developed. The method is based on a single-step, liquid-liquid extraction procedure, followed by isocratic reversed-phase high-performance liquid chromatography, with fluorescence detection. After extraction from 250 microliters plasma and 100 microliters urine, the limit of determination is 10 nM and 25 nM, respectively. For the use as standards, commercially available quinidine was purified from dihydroquinidine; Quinidine N-oxide was synthesized.
Pharmacokinetics of quinidine and three of its metabolites in man
J Pharmacokinet Biopharm 1984 Feb;12(1):1-21.PMID:6747817DOI:10.1007/BF01063608.
Disposition parameters of quinidine and three of its metabolism, 3-hydroxy quinidine, Quinidine N-oxide, and quinidine 10,11-dihydrodiol, were determined in five normal healthy volunteers after prolonged intravenous infusion and multiple oral doses. The plasma concentrations of individual metabolites after 7 hr of constant quinidine infusion at a plasma quinidine level of 2.9 +/- (SD) 0.3 mg/L were: 3-hydroxy quinidine, 0.32 +/- 0.06 mg/L; Quinidine N-oxide, 0.28 +/- 0.03 mg/L; and quinidine 10,11-dihydrodiol, 0.13 +/- 0.04 mg/L. Plasma trough levels after 12 oral doses of quinidine sulfate every 4 hr averaged: quinidine, 2.89 +/- 0.50 mg/L; 3-hydroxy quinidine, 0.83 +/- 0.36 mg/L; Quinidine N-oxide, 0.40 +/- 0.13 mg/L; and quinidine 10,11-dihydrodiol, 0.38 +/- 0.08 mg/L. Relatively higher plasma concentrations of 3-hydroxy quinidine metabolite after oral dosing probably reflect first-pass formation of this quinidine metabolite. A two-compartment model for quinidine and a one-compartment model for each of the metabolites described the plasma concentration-time curves for both i.v. infusion and multiple oral doses. Mean (+/- SD) disposition parameters for quinidine from individual fits, after i.v. infusion were as follows: Vl, 0.37 +/- 0.09 L/kg; lambda 1, 0.094 +/- 0.009 min-1; lambda 2, 0.0015 +/- 0.0002 min-1; EX2, 0.013 +/- 0.002 min-1; clearance (ClQ), 3.86 +/- 0.83 ml/min/kg. Both plasma and urinary data were used to determine metabolic disposition parameters. Mean (+/- SD) values for the metabolites after i.v. quinidine infusion were as follows: 3-hydroxy quinidine: formation rate constant kmf, 0.0012 +/- 0.0005 min-1, volume of distribution, Vm, 0.99 +/- 0.47 L/kg; and elimination rate constant, kmu 0.0030 +/- 0.0002 min-1. Quinidine N-oxide: kmf, 0.00012 +/- 0.00003 min-1; Vm, 0.068 +/- 0.020 L/kg; and kmu, 0.0063 +/- 0.0008 min-1. Quinidine 10,11-dihydrodiol: kmf, 0.0003 +/- 0.0001 min-1; Vm, 0.43 +/- 0.29 L/kg; and kmu, 0.0059 +/- 0.0010 min-1. Oral absorption of quinidine was described by a zero order process with a bioavailability of 0.78. Concentration dependent renal elimination of 3-hydroxy quinidine was observed in two out of five subjects studied.
Induction of quinidine metabolism and plasma protein binding by phenobarbital in dogs
J Pharmacokinet Biopharm 1984 Oct;12(5):495-515.PMID:6520745DOI:10.1007/BF01060128.
Two porta-caval transposed mongrel dogs were studied for phenobarbital (PB) induction of quinidine disposition after separate quinidine infusions via normal intravenous route and via portal vein. The plasma concentrations of quinidine and of three metabolites measured (3-OH quinidine, Quinidine N-oxide, quinidine 10,11-dihydrodiol) were quite similar between i.v. and portal vein infusions, suggesting that the liver extraction ratio for quinidine in dogs is very low. After PB pretreatment plasma quinidine concentrations at the end of a 10 hr infusion increased about twofold while the half-life decreased from a control value of about 16 hr to 6 hr. Plasma concentrations of the three major metabolites measured were also increased following PB treatment. Plasma protein binding for quinidine and two of its three measured metabolites (3-hydroxy quinidine and Quinidine N-oxide) were increased after PB treatment. Pharmacokinetic analysis of the data showed a decrease in steady-state volume of distribution (Vdss) of quinidine from an average value of 153 L to 54 L after PB treatment, while the total clearance did not change (6.6 vs. 5.6 L/hr). This decrease in Vdss could be explained by an increase in plasma protein binding of quinidine after PB treatment. The unbound nonrenal clearance of quinidine was induced by PB treatment. The decrease in fraction free in plasma and increase in unbound nonrenal (hence total) clearance resulted in little or no change in total plasma clearance for quinidine. The formation rate constants calculated for two quinidine metabolites, 3-hydroxy quinidine and Quinidine N-oxide, were increased after PB treatment, suggesting an induction in these two metabolic pathways. Only quinidine 10,11-dihydrodiol was found in the bile after quinidine infusion, and the biliary clearance of this metabolite was also induced after PB treatment.
Kinetics of microsomal metabolism of quinidine in rats
Res Commun Chem Pathol Pharmacol 1985 Jul;49(1):109-24.PMID:4035074doi
Kinetics of in vitro metabolism of quinidine was investigated using rat liver microsomes. Quinidine elimination was capacity limited with apparent Michaelis constant (appKM) of 2.6 microM (about 1.2 mg/L) in liver microsomes from uninduced rats. Phenobarbital (PB) pretreatment caused induction of quinidine metabolism. Formation of all three metabolites important in man, 3-hydroxyquinidine, Quinidine N-oxide and quinidine 10,11-dihydrodiol were PB inducible (Vmax increased). To study any direct interaction between PB and quinidine, PB was also added to the microsomal incubate and was found to decrease the rate constant for quinidine metabolism, suggesting inhibition of quinidine metabolism by PB. While, 3-hydroxyquinidine formation was inhibited (Vmax decreased and KM increased), the formation of Quinidine N-oxide was activated (Vmax increased). The formation of quinidine 10,11-dihydrodiol, although a minor metabolite in rat, was also inhibited in presence of PB. It is apparent from this study that PB when administered in vivo would act as both inducer and inhibitor of quinidine metabolism.
In vitro metabolism of quinidine: the (3S)-3-hydroxylation of quinidine is a specific marker reaction for cytochrome P-4503A4 activity in human liver microsomes
J Pharmacol Exp Ther 1999 Apr;289(1):31-7.PMID:10086984doi
The aim of this study was to evaluate the (3S)-3-hydroxylation and the N-oxidation of quinidine as biomarkers for cytochrome P-450 (CYP)3A4 activity in human liver microsome preparations. An HPLC method was developed to assay the metabolites (3S)-3-hydroxyquinidine (3-OH-Q) and Quinidine N-oxide (Q-N-OX) formed during incubation with microsomes from human liver and from Saccharomyces cerevisiae strains expressing 10 human CYPs. 3-OH-Q formation complied with Michaelis-Menten kinetics (mean values of Vmax and Km: 74.4 nmol/mg/h and 74.2 microM, respectively). Q-N-OX formation followed two-site kinetics with mean values of Vmax, Km and Vmax/Km for the low affinity isozyme of 15.9 nmol/mg/h, 76.1 microM and 0.03 ml/mg/h, respectively. 3-OH-Q and Q-N-OX formations were potently inhibited by ketoconazole, itraconazole, and triacetyloleandomycin. Isozyme specific inhibitors of CYP1A2, -2C9, -2C19, -2D6, and -2E1 did not inhibit 3-OH-Q or Q-N-OX formation, with Ki values comparable with previously reported values. Statistically significant correlations were observed between CYP3A4 content and formations of 3-OH-Q and Q-N-OX in 12 human liver microsome preparations. Studies with yeast-expressed isozymes revealed that only CYP3A4 actively catalyzed the (3S)-3-hydroxylation. CYP3A4 was the most active enzyme in Q-N-OX formation, but CYP2C9 and 2E1 also catalyzed minor proportions of the N-oxidation. In conclusion, our studies demonstrate that only CYP3A4 is actively involved in the formation of 3-OH-Q. Hence, the (3S)-3-hydroxylation of quinidine is a specific probe for CYP3A4 activity in human liver microsome preparations, whereas the N-oxidation of quinidine is a somewhat less specific marker reaction for CYP3A4 activity, because the presence of a low affinity enzyme is demonstrated by different approaches.