4-Hydroxyantipyrine
(Synonyms: 4-羟基安替比林,4-Hydroxyphenazone; NSC 174055) 目录号 : GC65523
4-Hydroxyantipyrine (4-Hydroxyphenazone; NSC 174055) 是安替比林 (Antipyrine) 的主要代谢产物，可作为生物分布促进剂。4-Hydroxyantipyrine 可增加胞磷胆碱和安替比林在脑内的浓度比分布。
Cas No.:1672-63-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
4-Hydroxyantipyrine (4-Hydroxyphenazone; NSC 174055) is the major metabolite of Antipyrine , can be as a biodistribution promoter. 4-Hydroxyantipyrine can increase distribution of concentration ratio of Citicoline and Antipyrine in the brain[1][2].
4-Hydroxyantipyrine increase the tissue-to-plasma concentration ratio of Citicoline in the brain and liver and that of thiopental sodium in the brain, liver, and heart[1].4-Hydroxyantipyrine enhances the blood-brain barrier (BBB) permeability of Antipyrine considering to be concerned with the increase of the Kp value of Antipyrine in the brain[2].
[1]. Ohkawa Y, et al. Effects of 4-hydroxyantipyrine and its 4-O-sulfate on antipyrine as biodistribution promoter. Biol Pharm Bull. 2001 May;24(5):529-34. [2]. Ohkawa Y, et al. Application of 4-hydroxyantipyrine and acetaminophen O-sulfate as biodistribution promoter. Biol Pharm Bull. 2001 Dec;24(12):1404-10.
| Cas No. | 1672-63-5 | SDF | Download SDF |
| 别名 | 4-羟基安替比林,4-Hydroxyphenazone; NSC 174055 | ||
| 分子式 | C11H12N2O2 | 分子量 | 204.23 |
| 溶解度 | 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 | 4.8964 mL | 24.4822 mL | 48.9644 mL |
| 5 mM | 0.9793 mL | 4.8964 mL | 9.7929 mL |
| 10 mM | 0.4896 mL | 2.4482 mL | 4.8964 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 |
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| % 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。
Effects of 4-Hydroxyantipyrine and its 4-O-sulfate on antipyrine as biodistribution promoter
Biol Pharm Bull 2001 May;24(5):529-34.PMID:11379775DOI:10.1248/bpb.24.529.
The effects of 4-Hydroxyantipyrine (4-OH), a major metabolite of antipyrine, and its 4-O-sulfate (4-S) on the pharmacokinetics of antipyrine were investigated in rats. Plasma elimination of intravenously administered antipyrine was significantly decelerated under a steady-state concentration of 4-OH but not under that of 4-S. Tissue-to-plasma concentration ratio (Kp) of antipyrine under its steady-state concentration was significantly increased in the brain and heart by the concomitant use of 4-OH, while similar use of 4-S had no effect. The enhancement of the blood-brain barrier (BBB) permeability of antipyrine caused by the concomitant use of 4-OH was believed to be concerned with the increase of the Kp value of antipyrine in the brain. These results suggested that 4-OH could be used as a biodistribution promoter.
Application of 4-Hydroxyantipyrine and acetaminophen O-sulfate as biodistribution promoter
Biol Pharm Bull 2001 Dec;24(12):1404-10.PMID:11767111DOI:10.1248/bpb.24.1404.
The effects of 4-Hydroxyantipyrine (4-OH), a major metabolite of antipyrine and its sulfate, 4-Hydroxyantipyrine O-sulfate (4-S), on the pharmacokinetics of citicoline and thiopental sodium were investigated in rats. The concomitant use of 4-OH increased significantly the tissue-to-plasma concentration ratio (Kp) of citicoline in the brain and liver and that of thiopental sodium in the brain, liver, and heart, while 4-S did not affect them. The permeability clearance of blood-brain barrier (BBB) (Kin) and the total distribution volume (Vdbr) of citicoline were not affected by either 4-OH or 4-S. However, those of thiopental sodium were significantly increased by not only 4-OH but also by 4-S. On the other hand, the plasma concentration of antipyrine was significantly decreased by the intravenous bolus coadministration of N-acetyl-p-aminophenyl O-sulfate (APAPS) at steady-state plasma concentration of antipyrine. A similar reduction was not observed with the intravenous coadministration of acetaminophen (APAP). The Kp value of antipyrine was significantly increased in the brain by the coadministration of APAPS, but was not affected by APAP. The increment in the drug distribution to the brain with the concomitant use of 4-OH (or APAPS) observed in this study is useful information for the application of drug combinations as biodistribution promoters.
Antipyrine as a probe for human oxidative drug metabolism: identification of the cytochrome P450 enzymes catalyzing 4-Hydroxyantipyrine, 3-hydroxymethylantipyrine, and norantipyrine formation
Clin Pharmacol Ther 1996 Jun;59(6):613-23.PMID:8681486DOI:10.1016/S0009-9236(96)90001-6.
Background and objective: Antipyrine has been widely used as a probe drug for human oxidative drug metabolism. To evaluate the role of antipyrine as a model drug, we have identified the cytochrome P450 enzymes involved in 4-Hydroxyantipyrine, 3-hydroxymethylantipyrine, and norantipyrine formation. Methods: We used the following methods for this study: (1) determination of enzyme kinetics for antipyrine metabolite formation in human liver microsomes, (2) inhibition studies with antibodies and inhibitors, and (3) formation of metabolites by stable expressed human P450 enzymes. Results: Antipyrine biotransformation could be described by Michaelis-Menten kinetics: norantipyrine: maximum rate of metabolite formation (Vmax), 0.91 +/- 0.04 nmol . mg-1 . min-1; Michaelis-Menten constant (Km), 19.0 +/- 0.8 mmol/L; 4-Hydroxyantipyrine: Vmax, 1.54 +/- 0.08 nmol . mg-1 . min-1;Km,39.6 +/- 2.5 mmol/L. Antibodies against CYP3A4 inhibited the formation of 4-Hydroxyantipyrine by 25% to 65%. LKM-2 antibodies (anti-CYP2C) caused a 75% to 100% inhibition of norantipyrine and a 58% to 80% inhibition of 3-hydroxymethylantipyrine formation. Sulfaphenazole inhibited the formation of 3-hydroxymethylantipyrine and norantipyrine by about 50%. Furafylline and fluvoxamine inhibited norantipyrine, 4-Hydroxyantipyrine, and 3-hydroxymethylantipyrine formation by about 30%, 30%, and 50%, respectively. Ketoconazole reduced formation of norantipyrine, 3-hydroxymethylantipyrine, and 4-Hydroxyantipyrine by up to 80%. Formation in stable expressed enzymes indicated involvement of CYP1A2, CYP2B6, CYP2C, and CYP3A4 in metabolite formation. Conclusion: Antipyrine metabolites are formed by at least six hepatic cytochrome P450 enzymes (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C18, and CYP3A4). 4-Hydroxylation is mainly catalyzed by CYP3A4 and, to a lesser extent, by CYP1A2. The CYP2C subfamily contains the predominant enzymes for norantipyrine formation, and CYP1A2 is also involved. Formation of 3-hydroxymethylantipyrine is mediated by CYP1A2 and CYP2C9. Because several cytochrome P450 enzymes are involved in the formation of each metabolite, antipyrine is not well suited as a probe for distinct human cytochrome P450 enzymes.
Separation and identification of the 4-Hydroxyantipyrine sulphoconjugate
J Chromatogr 1992 Apr 15;576(1):103-9.PMID:1500444DOI:10.1016/0378-4347(92)80180-x.
In a previous study we observed, during separation of total antipyrine metabolites by high-performance liquid chromatography and after enzymatic hydrolysis, an unidentified peak corresponding to an ionic compound with pyrazolinone features. In the present study, this compound was identified as the 4-Hydroxyantipyrine sulphoconjugate, and its structure was definitively confirmed by gas chromatographic-mass spectrometric analysis and by the use of pure synthetic substance. We also demonstrated the inhibitory effect of sodium metabisulphite, a necessary preservative of urinary samples, on hydrolysis of this conjugate in the presence of sulphatases from Helix pomatia or Aerobacter aerogenes. This inhibitory effect makes it impossible to perform a global assay of antipyrine metabolites after enzymatic or chemical hydrolysis and confirms the value of direct assay of the 4-Hydroxyantipyrine sulphoconjugate.
Simultaneous determination of antipyrine, 4-Hydroxyantipyrine, 3-hydroxymethylantipyrine and norantipyrine in urine by gas chromatography chemical ionization mass spectrometry
Biomed Mass Spectrom 1982 Oct;9(10):425-8.PMID:7171741DOI:10.1002/bms.1200091004.
A simple, accurate and precise procedure was developed to quantify, in a single run, antipyrine, 4-Hydroxyantipyrine, 3-hydroxymethylantipyrine and norantipyrine in urine. The stable isotope-labelled internal standards for the assay were obtained from a subject who ingested deuterium labelled antipyrine and produced urine containing the labelled drug and metabolites.