Norverapamil hydrochloride ((±)-Norverapamil hydrochloride)
(Synonyms: 盐酸去甲维拉帕米; (±)-Norverapamil hydrochloride; D591 hydrochloride) 目录号 : GC32518
An L-type calcium channel blocker
Cas No.:67812-42-4
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
Norverapamil is the N-demethylated metabolite of verapamil , an L-type calcium channel blocker and P-glycoprotein inhibitor. It is the major active metabolite of verapamil with approximately 20% efficacy of its parent with regard to vasodilatory activity.1 Norverapamil has been shown to inhibit mycobacterial efflux pumps and the expansion of M. tuberculosis-specific T cells.2
1.Tracy, T.S., Korzekwa, K.R., Gonzalez, F.J., et al.Cytochrome P450 isoforms involved in metabolism of the enantiomers of verapamil and norverapamilBr. J. Clin. Pharmacol.47(5)545-552(1999) 2.Abate, G., Ruminiski, P.G., Kumar, M., et al.New verapamil analogs inhibit intracellular mycobacteria without affecting the functions of Mycobacterium-specific T cellsAntimicrob. Agents Chemother.60(3)1216-1225(2015)
| Cas No. | 67812-42-4 | SDF | |
| 别名 | 盐酸去甲维拉帕米; (±)-Norverapamil hydrochloride; D591 hydrochloride | ||
| Canonical SMILES | N#CC(C(C)C)(CCCNCCC1=CC=C(OC)C(OC)=C1)C2=CC=C(OC)C(OC)=C2.[H]Cl | ||
| 分子式 | C26H37ClN2O4 | 分子量 | 477.04 |
| 溶解度 | DMSO : ≥ 31 mg/mL (64.98 mM) | 储存条件 | 4°C, protect from light |
| 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 | 2.0963 mL | 10.4813 mL | 20.9626 mL |
| 5 mM | 0.4193 mL | 2.0963 mL | 4.1925 mL |
| 10 mM | 0.2096 mL | 1.0481 mL | 2.0963 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 Verapamil Hydrochloride and Norverapamil hydrochloride in Rat Plasma by Capillary Electrophoresis With End-Column Electrochemiluminescence Detection and Their Pharmacokinetics Study
J Chromatogr Sci 2021 Feb 15;59(3):289-296.PMID:33333557DOI:10.1093/chromsci/bmaa098.
In this study, we developed a new method for simultaneous determination of verapamil hydrochloride (VerHCl) and its metabolite Norverapamil hydrochloride (NorHCl) by using the capillary electrophoresis-electrochemiluminescence. Under optimized experimental conditions, the linear ranges of the VerHCl and NorHCl concentrations were 0.015-10.0 and 0.060-10.0 μg/mL, respectively. The linearity relations were determined using the respective regression equations y = 581.2x + 19.94 and y = 339.4x + 29.16. The respective limits of detection (S/N = 3) were 0.006 and 0.024 μg/mL. The proposed method was used to study the pharmacokinetics of both agents in rat plasma. The maximum concentration (Cmax), half-life time (T1/2) and time to peak (Tmax) were 683.21 ± 74.81 ng/mL, 0.52 ± 0.21 h and 2.49 ± 0.32 h for VerHCl and 698.42 ± 71.45 ng/mL, 1.14 ± 0.26 h and 2.83 ± 0.23 h for NorHCl, respectively, following oral administration of 10 mg/kg VerHCl.
Verapamil and Norverapamil determination in human plasma by gas-liquid chromatography using nitrogen-phosphorus detection: application to single-dose pharmacokinetic studies
Pharmacology 1984;29(5):264-8.PMID:6494236DOI:10.1159/000138022.
A sensitive (to 0.5 ng/ml) and specific method for the determination of verapamil and Norverapamil which utilizes gas-liquid chromatography with nitrogen-phosphorus detection is described. A basic extraction with acid back-wash and final basic reextraction is used for the preparation of plasma samples. Standard curves using alpha-isopropyl-alpha-[(N-methyl-N-homoveratryl)-beta-aminoethyl]- 3,4- dimethoxyphenylacetonitrile hydrochloride (D-517) are linear for concentrations from 0.5 to 200 ng/ml for both verapamil and Norverapamil. Within-day and between-day reproducibility is good with a coefficient of variation less than 10% for all concentrations. Recovery is complete for both verapamil and Norverapamil. Application of the method is demonstrated by a pharmacokinetic study in a normal volunteer who received 10 mg verapamil hydrochloride by intravenous infusion.
Simultaneous analysis of the enantiomers of verapamil and Norverapamil in rat plasma by liquid chromatography-tandem mass spectrometry
J Pharm Biomed Anal 2007 Dec 21;45(5):762-8.PMID:17981422DOI:10.1016/j.jpba.2007.09.021.
An enantioselective micromethod for the simultaneous analysis of verapamil (VER) and Norverapamil (NOR) in plasma was developed, validated and applied to the study of the kinetic disposition of VER and NOR after the administration of a single oral dose of racemic-VER to rats. VER, NOR and the internal standard (paroxetine) were extracted from only 100-microL plasma samples using n-hexane and the enantiomers were resolved on a Chiralpak AD column using n-hexane:isopropanol:ethanol:diethylamine (88:6:6:0.1) as the mobile phase. The analyses were performed in the selected reaction monitoring mode. Transitions 456>166 for VER enantiomers, 441>166 for NOR enantiomers and 330>193 for the internal standard were monitored and the method had a total chromatographic run time of 12 min. The method allows the determination of VER and NOR enantiomers at plasma levels as low as 1.0 ng/mL. Racemic VER hydrochloride (10mg/kg) was given to male Wistar rats by gavage and blood samples were collected from 0 to 6.0 h (n=6 at each time point). The concentration of (-)-(S)-VER was three folds higher than (+)-(R)-VER, with an AUC ratio (-)/(+) of 2.66. Oral clearance values were 12.17 and 28.77 L/h/kg for (-)-(S)-VER and (+)-(R)-VER, respectively. The pharmacokinetic parameters of NOR were not shown to be enantioselective.
Metabolite parameters as an appropriate alternative approach for assessment of bioequivalence of two verapamil formulations
Iran J Pharm Res 2014 Spring;13(2):383-9.PMID:25237334doi
A bioequivalence study of two verapamil formulations (generic verapamil tablets and Isoptin(®) tablets) was performed by comparing pharmacokinetic parameters of the parent drug and its major metabolite, Norverapamil following a single dose administration of 80 mg verapamil hydrochloride in 22 healthy volunteers according to a randomized, two-period, crossover-design study. Moreover, the feasibility of proving bioequivalence of verapamil oral dosing form by means of Norverapamil pharmacokinetic parameters was evaluated. Concentrations of verapamil and Norverapamil were quantified in plasma using a validated high-performance liquid chromatography (HPLC) with fluorescence detection. The 90% CIs for the log-transformed ratios of verapamil Cmax (maximum plasma concentration) and AUC0-∿area under the plasma concentration-versus-time curve from time zero to the infinity) were 73 to 101 and 80 to 103, respectively. Similarly, the corresponding ranges for Norverapamil were 80-100 and 84-103, respectively. According to the parent drug data, the 90% confidence intervals around the geometric mean ratio of AUC happened to fit within preset bioequivalence limits of 80-125%, whereas those for Cmax did not. The 90% confidence intervals for both Cmax and AUC of Norverapamil met preset bioequivalence limits. The AUC and Cmax of metabolite, when compared to parent drug, showed a much lower degree of variability and the 90% confidence intervals of the metabolite were therefore narrower than those of the parent drug. These observations indicate that bioequivalence studies using metabolite, Norverapamil, could be a more suitable and preferable approach to assess bioequivalence of verapamil formulations due to its much lower variability and therefore lower number of volunteers that are required to conduct the study.
Bioequivalence of verapamil hydrochloride extended-release pellet-filled capsules when opened and sprinkled on food and when swallowed intact
Clin Pharm 1992 Jun;11(6):539-42.PMID:1600686doi
A study was performed to determine whether verapamil hydrochloride administered in extended-release pellet-filled capsules is bioequivalent to the same formulation administered by sprinkling the contents of the capsules onto food. Thirty-two healthy subjects participated in the randomized, two-way crossover study. In treatment A, the subjects swallowed the contents of a verapamil hydrochloride extended-release pellet-filled capsule, 240 mg, that had been sprinkled on applesauce. In treatment B, the subjects swallowed the same type of capsule intact. Blood samples were drawn at baseline, every hour for 10 hours, and at 12, 15, 24, 30, 36, and 48 hours after each dose administration. The plasma was analyzed for verapamil and Norverapamil by high-performance liquid chromatography. The following calculations were performed: AUC0-48, AUC0-infinity, Cmax, tmax, and k. Results for the two treatments were compared by analysis of variance. There were no significant differences between the AUC0-48, AUC0-infinity, Cmax, tmax, and k for the two methods of dose administration. For verapamil the differences for all variables were less than 5%, and for Norverapamil the differences were less than 4% for all variables except tmax (9.5%). The 90% confidence intervals were within acceptable limits for all variables except the Norverapamil tmax comparison. Sprinkling the contents of extended-release pellet-filled capsules onto food provides verapamil hydrochloride that is bioequivalent to that obtained from the intact capsules.