N-Desmethyl Sildenafil
(Synonyms: N-去甲基西地那非,Desmethylsildenafil; UK-103,320) 目录号 : GC44350
A major metabolite of sildenafil
Cas No.:139755-82-1
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
N-Desmethyl sildenafil is a major metabolite of sildenafil . N-Desmethyl sildenafil is formed via oxidative metabolism of sildenafil by the cytochrome (CYP) P450 isoforms CYP3A4, CYP3A5, and CYP3A7.
| Cas No. | 139755-82-1 | SDF | |
| 别名 | N-去甲基西地那非,Desmethylsildenafil; UK-103,320 | ||
| Canonical SMILES | CCOC1=C(C2=NC(C(CCC)=NN3C)=C3C(N2)=O)C=C(C=C1)S(N4CCNCC4)(=O)=O | ||
| 分子式 | C21H28N6O4S | 分子量 | 460.6 |
| 溶解度 | DMF: 5 mg/ml,DMSO: 10 mg/ml,DMSO:PBS (pH 7.2)(1:5): 0.15 mg/ml | 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 | 2.1711 mL | 10.8554 mL | 21.7108 mL |
| 5 mM | 0.4342 mL | 2.1711 mL | 4.3422 mL |
| 10 mM | 0.2171 mL | 1.0855 mL | 2.1711 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。
UPLC-MS/MS for the Simultaneous Determination of Sildenafil and N-Desmethyl Sildenafil
J Chromatogr Sci 2021 Sep 29;59(9):823-829.PMID:33517421DOI:10.1093/chromsci/bmaa138.
A sensitive high-performance liquid chromatography-tandem mass spectrometry method was established for the simultaneous determination of sildenafil and N-Desmethyl Sildenafil in human plasma. The protein precipitation was used for extraction and the gradient elution of the mobile phase A of water (containing 0.01% formic acid) and the mobile phase B of acetonitrile, and methanol (V:V = 1:1, containing 0.01% formic acid) was used for chromatographic separation on a C18 column. Quantification was performed by multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 475.4 → m/z 283.3 for sildenafil, m/z 461.4 → m/z 283.2 for N-Desmethyl Sildenafil, m/z 483.3 → m/z 108.1 for sildenafil-d8 (IS) and m/z 469.2 → m/z 283.3 for N-desmethyl sildenafil-d8 (IS) at the positive ionization mode. The intra- and inter-day relative standard deviations were less than 6.8% and 4.1% for sildenafil and N-Desmethyl Sildenafil, respectively. Accuracy at four levels ranged from 93.1% to 115.9% for sildenafil and 95.6% to 112.5% for N-Desmethyl Sildenafil. The present method was sensitive and reliable for simultaneous quantification of sildenafil and its active metabolite and was successfully applied to a pharmacokinetic study of an oral low dose of sildenafil in Chinese healthy volunteers.
A UPLC-MS/MS method for simultaneous quantification of sildenafil and N-Desmethyl Sildenafil applied in pharmacokinetic and bioequivalence studies in a Chinese population
Int J Clin Pharmacol Ther 2021 Feb;59(2):164-174.PMID:33210997DOI:10.5414/CP203838.
Objective: To evaluate the pharmacokinetic parameters and bioequivalence of two sildenafil tablets (20 mg) in healthy Chinese subjects. Materials and methods: A random, crossover, self-control design was used. 20 healthy subjects including males and females were randomized into two groups. A single oral dose of the trial or reference preparation was given to the two groups of subjects after an overnight fast of 10 hours. Blood samples were taken at scheduled time points. Plasma concentrations of sildenafil and N-Desmethyl Sildenafil were measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). ANOVA was used to check the difference of the mean values of the pharmacokinetic parameters between the two preparations. Bioequivalence was determined by two one-sided t-tests and 90% confidence intervals. Results: The quantitative range of sildenafil and N-Desmethyl Sildenafil was 2.000 - 200.0 ng/mL and 0.800 - 80.00 ng/mL, respectively. Plasma samples were stable, and there was no mutual interference between the analyte and internal standard. With the 90% confidence limit, the trial preparations AUC0→t and Cmax fall within 80.00 - 125.00% of the reference preparation's AUC0→t and Cmax. The tmax of sildenafil and N-Desmethyl Sildenafil was ~ 0.9 hours and 1 hour, and the T1/2 was 2.4 hours and 3.7 hours, respectively. The relative bioavailability of sildenafil and N-Desmethyl Sildenafil was 99.28 ± 3.30% and 99.20 ± 3.39%. No significant difference was found in every factor between the trial preparation and the reference preparation. Conclusion: The UPLC-MS/MS method was successfully established to evaluate the pharmacokinetic parameters of sildenafil in healthy Chinese subjects. The trial preparation was bioequivalent to the reference preparation.
Simultaneous quantification of sildenafil and N-Desmethyl Sildenafil in human plasma by UFLC coupled with ESI-MS/MS and pharmacokinetic and bioequivalence studies in Malay population
Biomed Chromatogr 2015 Jun;29(6):953-60.PMID:25400284DOI:10.1002/bmc.3378.
A simple, rapid, specific and reliable UFLC coupled with ESI-MSMS assay method to simultaneously quantify sildenafil and N-Desmethyl Sildenafil, with loperamide as internal standard, was developed. Chromatographic separation was performed on a Thermo Scientific Accucore C18 column with an isocratic mobile phase composed of 0.1% v/v formic acid in purified water-methanol (20:80, v/v), at a flow rate of 0.3 mL/min. Sildenafil, N-Desmethyl Sildenafil and loperamide were detected with proton adducts at m/z 475.4 > 58.2, 461.3 > 85.2 and 477.0 > 266.1 in multiple reaction monitoring positive mode, respectively. Both analytes and internal standard were extracted by diethyl ether. The method was validated over a linear concentration range of 10-800 ng/mL for sildenafil and 10-600 ng/mL for N-Desmethyl Sildenafil with correlation coefficient (r(2) ) ≥0.9976 for sildenafil and (r(2) ) ≥0.9992 for N-Desmethyl Sildenafil. The method was precise, accurate and stable. The proposed method was applied to study the bioequivalence between a 100 mg dose of two pharmaceutical products: Viagra (original) and Edyfil (generic) products. AUC0-t , Cmax and Tmax were 2285.79 ng h/mL, 726.10 ng/mL and 0.94 h for Viagra and 2363.25 ng h/mL, 713.91 ng/mL and 0.83 hour for Edyfil. The 90% confidence interval of these parameters of this study fall within the regulatory range of 80-125%, hence they are considered as bioequivalent.
Reverse-phase high-performance liquid chromatography for the simultaneous determination of sildenafil and N-Desmethyl Sildenafil in plasma of children
Biomed Chromatogr 2016 Dec;30(12):2070-2073.PMID:27215176DOI:10.1002/bmc.3765.
Sildenafil is a selective inhibitor of cGMP-specific type 5 phosphodiesterase used for the treatment of pulmonary arterial hypertension (PAH) in the adults. In pediatrics, PAH treatment options include the off-label use of sildenafil. Sildenafil is metabolized in the liver by cytocrome P450 into its active metabolite, N-Desmethyl Sildenafil. The determination of plasma levels of sildenafil and N-Desmethyl Sildenafil could be useful for therapy optimization and pharmacokinetic studies. We have developed and validated a method for the quantification of sildenafil and its metabolite in plasma of children by rapid extraction, using high-performance liquid chromatography with ultraviolet detection. The calibration range was fitted at least square model (r2 ≥ 0.999), with an accuracy and an intra- and inter-day relative standard deviation <15% for both analytes. The mean recovery was 102.5% for sildenafil and 101.8% for N-Desmethyl Sildenafil. This simple method could be successfully used in children with PAH under treatment with sildenafil.
Development and validation of an ultra performance liquid chromatography tandem mass method for sildenafil and N-Desmethyl Sildenafil plasma determination and quantification
J Chromatogr B Analyt Technol Biomed Life Sci 2015 Sep 15;1001:35-40.PMID:26253809DOI:10.1016/j.jchromb.2015.07.023.
Sildenafil is a selective inhibitor of cGMP-specific type 5 phosphodiesterase (PDE5) used for the treatment of masculine erectile dysfunction and Pulmonary Arterial Hypertension (PAH). Sildenafil causes vasodilatation; relax of the smooth muscle and reduction of pulmonary arterial pressure. In the liver cytocrome P450 metabolizes sildenafil into its active metabolite, N-Desmethyl Sildenafil. The determination of plasma levels of sildenafil and N-Desmethyl Sildenafil could be useful for therapy optimization and pharmacokinetic studies. We have developed and validated a new method for the quantification of sildenafil and its metabolite in human plasma by rapid protein precipitation extraction, using an UPLC system, coupled with a tandem mass spectrometric detector (UPLC-MS/MS). The calibration range was fitted at least square model (r(2)≥0.999), with an accuracy and an intra- and inter-day RSD% (Relative Standard Deviation), both for sildenafil and N-Desmethyl Sildenafil, lower than 15%, as required by the FDA guidelines; LLOQ, LLOD, ULOQ were 3.9ng/mL, 1.95ng/mL and 1000ng/mL, respectively, for both analytes. Matrix effect, expressed as mean percent deviation of peak areas, was in the range between 2.6% and 5.8%, lower than 15% as required by guidelines. The mean recovery was 83.2 % for sildenafil and 84.5% for N-Desmethyl Sildenafil. This method has successfully been applied to a clinical pharmacokinetic study of sildenafil and N-Desmethyl Sildenafil in patients with PAH undergoing cardiac surgery.