Hydroxymetronidazole
(Synonyms: 羟基甲硝唑,Metronidazole-OH) 目录号 : GC49832
An active metabolite of metronidazole
Cas No.:4812-40-2
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
Hydroxymetronidazole is an active metabolite of the antibiotic metronidazole .1 It is formed from metronidazole primarily by the cytochrome P450 (CYP) isoform CYP2A6.2 Hydroxymetronidazole is active against B. fragilis, B. thetaiotaomicron, B. distasonis, and B. ovatus (MICs = 1, 2, 1, and 2 µg/ml, respectively).1 It has been found in pork and porcine plasma.3
1.Pendland, S.L., Piscitelli, S.C., Schreckenberger, P.C., et al.In vitro activities of metronidazole and its hydroxy metabolite against Bacteroides sppAntimicrob. Agents Chemother.38(9)2106-2110(1994) 2.Pearce, R.E., Cohen-Wolkowiez, M., Sampson, M.R., et al.The role of human cytochrome P450 enzymes in the formation of 2-hydroxymetronidazole: CYP2A6 is the high affinity (low Km) catalystDrug Metab. Dispos.41(9)1686-1694(2013) 3.TÖlgyesi, A., Sharma, V.K., Fekete, S., et al.Development of a rapid method for the determination and confirmation of nitroimidazoles in six matrices by fast liquid chromatography-tandem mass spectrometryJ. Pharm. Biomed. Anal.64-6540-48(2012)
| Cas No. | 4812-40-2 | SDF | Download SDF |
| 别名 | 羟基甲硝唑,Metronidazole-OH | ||
| Canonical SMILES | OCC1=NC=C([N+]([O-])=O)N1CCO | ||
| 分子式 | C6H9N3O4 | 分子量 | 187.2 |
| 溶解度 | DMSO: slightly soluble,Methanol: slightly soluble | 储存条件 | -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 | 5.3419 mL | 26.7094 mL | 53.4188 mL |
| 5 mM | 1.0684 mL | 5.3419 mL | 10.6838 mL |
| 10 mM | 0.5342 mL | 2.6709 mL | 5.3419 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。
Metronidazole and Hydroxymetronidazole central nervous system distribution: 2. cerebrospinal fluid concentration measurements in patients with external ventricular drain
Antimicrob Agents Chemother 2014;58(2):1024-7.PMID:24277050DOI:10.1128/AAC.01762-13.
This study explored metronidazole and Hydroxymetronidazole distribution in the cerebrospinal fluid (CSF) of brain-injured patients. Four brain-injured patients with external ventricular drain received 500 mg of metronidazole over 0.5 h every 8 h. CSF and blood samples were collected at steady state over 8 h, and the metronidazole and Hydroxymetronidazole concentrations were assayed by high-pressure liquid chromatograph. A noncompartmental analysis was performed. Metronidazole is distributed extensively within CSF, with a mean CSF to unbound plasma AUC0-τ ratio of 86% ± 16%. However, the concentration profiles in CSF were mostly flat compared to the plasma profiles. Hydroxymetronidazole concentrations were much lower than those of metronidazole both in plasma and in CSF, with a corresponding CSF/unbound plasma AUC0-τ ratio of 79% ± 16%. We describe here for the first time in detail the pharmacokinetics of metronidazole and Hydroxymetronidazole in CSF.
The effect of omeprazole on the pharmacokinetics of metronidazole and Hydroxymetronidazole in human plasma, saliva and gastric juice
Br J Clin Pharmacol 1997 Sep;44(3):245-53.PMID:9296318DOI:10.1046/j.1365-2125.1997.t01-1-00572.x.
Aims: To evaluate the effect of omeprazole on the pharmacokinetics of metronidazole and Hydroxymetronidazole in plasma, gastric juice and saliva following intravenous infusion or oral dosing of metronidazole. Methods: Eight volunteers received single doses of metronidazole (400 mg) intravenously and orally, whilst taking placebo or omeprazole (40 mg, twice daily for 5 days) in a randomized 4-way crossover study. Metronidazole and Hydroxymetronidazole concentrations in plasma, saliva and gastric juice samples were determined by h.p.l.c. Pharmacokinetic parameters for metronidazole and Hydroxymetronidazole were calculated, and the significance of the mean differences in parameters between omeprazole and placebo co-administration was assessed using a two-tailed, paired t-test. Results: There were no significant differences (P < 0.05) in any of the plasma or saliva pharmacokinetic parameter values for metronidazole between volunteers receiving omeprazole or placebo when metronidazole was administered either as an intravenous infusion or orally. Following intravenous administration of metronidazole to the placebo group and omeprazole treated group respectively, the gastric transfer of metronidazole was significantly reduced from 15.5 +/- 10.4% to 2.6 +/- 1.0% of the dose (P = 0.007; 95% CI of difference 4.8 to 21.0) with concomitant changes in the metronidazole AUC (from 77.5 +/- 18.0 mumol l-1 h to 352.6 +/- 182.1 mumol l-1 h; P = 0.0003; 95% CI of difference 127.6 to 422.7), Cmax (from 61.4 +/- 26.5 mumol l-1 to 271.8 +/- 104.3 mumol l-1; p = 0.0001; 95% CI of difference 118.6 to 302.1). Similarly, the gastric juice AUC of Hydroxymetronidazole was significantly reduced from 3.2 +/- 1.9 mumol l-1 h to 1.5 +/- 0.8 mumol l-1 h of the dose (P = 0.0043; 95% CI of difference 0.4 to 3.0) with a concomitant change in Cmax (from 5.0 +/- 2.5 mumol l-1 to 3.0 +/- 1.2 mumol l-1; P = 0.0007; 95% CI of difference 0.7 to 3.4). Conclusions: Omeprazole had little effect on the plasma and salivary pharmacokinetics of metronidazole (or its hydroxymetabolite) after intravenous or oral administration, but it did have a substantial effect on the pharmacokinetics of metronidazole and Hydroxymetronidazole in gastric juice.
In-vitro synergy of paromomycin with metronidazole alone or metronidazole plus Hydroxymetronidazole against Helicobacter pylori
J Antimicrob Chemother 1999 Mar;43(3):403-6.PMID:10223597DOI:10.1093/jac/43.3.403.
The in-vitro activities of paromomycin and metronidazole alone or paromomycin and metronidazole plus Hydroxymetronidazole (2:1 ratio) were studied against 19 Helicobacter pylori isolates using an in-vitro chequerboard technique. Partial synergy was demonstrated for the majority of isolates (11/19) for both combinations tested. When Hydroxymetronidazole was added to the parent compound, the number of metronidazole-sensitive isolates demonstrating synergy increased to 5/12, compared with 1/12 for the combination that did not include the metabolite. In metronidazole-resistant isolates there was a shift from an additive effect to partial synergy for the combination containing Hydroxymetronidazole. The in-vitro activity of paromomycin and the synergic effect that is achieved in combination with metronidazole and Hydroxymetronidazole render paromomycin suitable for further investigation as a treatment option for H. pylori infection.
Metronidazole and Hydroxymetronidazole central nervous system distribution: 1. microdialysis assessment of brain extracellular fluid concentrations in patients with acute brain injury
Antimicrob Agents Chemother 2014;58(2):1019-23.PMID:24277041DOI:10.1128/AAC.01760-13.
The distribution of metronidazole in the central nervous system has only been described based on cerebrospinal fluid data. However, extracellular fluid (ECF) concentrations may better predict its antimicrobial effect and/or side effects. We sought to explore by microdialysis brain ECF metronidazole distribution in patients with acute brain injury. Four brain-injured patients monitored by cerebral microdialysis received 500 mg of metronidazole over 0.5 h every 8 h. Brain dialysates and blood samples were collected at steady state over 8 h. Probe recoveries were evaluated by in vivo retrodialysis in each patient for metronidazole. Metronidazole and OH-metronidazole were assayed by high-pressure liquid chromatography, and a noncompartmental pharmacokinetic analysis was performed. Probe recovery was equal to 78.8% ± 1.3% for metronidazole in patients. Unbound brain metronidazole concentration-time curves were delayed compared to unbound plasma concentration-time curves but with a mean metronidazole unbound brain/plasma AUC0-τ ratio equal to 102% ± 19% (ranging from 87 to 124%). The unbound plasma concentration-time profiles for OH-metronidazole were flat, with mean average steady-state concentrations equal to 4.0 ± 0.7 μg ml(-1). This microdialysis study describes the steady-state brain distribution of metronidazole in patients and confirms its extensive distribution.
Liquid chromatography-tandem mass spectrometry for the simultaneous quantitation of ceftriaxone, metronidazole and Hydroxymetronidazole in plasma from seriously ill, severely malnourished children
Wellcome Open Res 2017 Jun 19;2:43.PMID:29479566DOI:10.12688/wellcomeopenres.11728.2.
We have developed and validated a novel, sensitive, selective and reproducible reversed-phase high-performance liquid chromatography method coupled with electrospray ionization mass spectrometry (HPLC-ESI-MS/MS) for the simultaneous quantitation of ceftriaxone (CEF), metronidazole (MET) and Hydroxymetronidazole (MET-OH) from only 50 µL of human plasma, and unbound CEF from 25 µL plasma ultra-filtrate to evaluate the effect of protein binding. Cefuroxime axetil (CEFU) was used as an internal standard (IS). The analytes were extracted by a protein precipitation procedure with acetonitrile and separated on a reversed-phase Polaris 5 C18-Analytical column using a mobile phase composed of acetonitrile containing 0.1% (v/v) formic acid and 10 mM aqueous ammonium formate pH 2.5, delivered at a flow-rate of 300 µL/min. Multiple reaction monitoring was performed in the positive ion mode using the transitions m/z555.1→ m/z396.0 (CEF), m/z172.2→ m/z 128.2 (MET), m/z188.0→ m/z125.9 (MET-OH) and m/z528.1→ m/z 364.0 (CEFU) to quantify the drugs. Calibration curves in spiked plasma and ultra-filtrate were linear ( r 2 ≥ 0.9948) from 0.4-300 µg/mL for CEF, 0.05-50 µg/mL for MET and 0.02 - 30 µg/mL for MET-OH. The intra- and inter- assay precisions were less than 9% and the mean extraction recoveries were 94.0% (CEF), 98.2% (MET), 99.6% (MET-OH) and 104.6% (CEF in ultra-filtrate); the recoveries for the IS were 93.8% (in plasma) and 97.6% (in ultra-filtrate). The validated method was successfully applied to a pharmacokinetic study of CEF, MET and MET-OH in hospitalized children with complicated severe acute malnutrition following an oral administration of MET and intravenous administration of CEF over the course of 72 hours.