Aliskiren-d6 (hemifumarate)
(Synonyms: CGP 60536 D6 hemifumarate; CGP60536B D6 hemifumarate; SPP 100 D6 hemifumarate) 目录号 : GC48407
An internal standard for the quantification of aliskiren
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Aliskiren-d6 is intended for use as an internal standard for the quantification of aliskiren by GC- or LC-MS. Aliskiren is a nonpeptide inhibitor of renin (IC50 = 0.6 nM for the human enzyme).1 Aliskiren (10 and 30 mg/kg per day) reduces blood pressure and prevents albuminuria in renin-overexpressing TG(mRen-2)27 rats in a model of streptozotocin-induced diabetes.2 It also reduces cardiac hypertrophy and fibrosis induced by heart pressure overload in mice.3 Formulations containing aliskiren have been used in the treatment of hypertension.
1.Rhuel, R., Rasetti, V., Maibaum, J., et al.Structure-based drug design: The discovery of novel nonpeptide orally active inhibitors of human reninChem. Biol.7(7)493-504(2000) 2.Feldman, D.L., Jin, L., Xuan, H., et al.Effects of aliskiren on blood pressure, albuminuria, and (pro)renin receptor expression in diabetic TG(mRen-2)27 ratsHypertension52(1)130-136(2008) 3.Weng, L., Zhang, W., Ye, Y., et al.Aliskiren ameliorates pressure overload-induced heart hypertrophy and fibrosis in miceActa Pharmacol. Sin.35(8)1005-1014(2014)
| Cas No. | SDF | ||
| 别名 | CGP 60536 D6 hemifumarate; CGP60536B D6 hemifumarate; SPP 100 D6 hemifumarate | ||
| Canonical SMILES | COC1=C(OCCCOC)C=C(C[C@H](C(C)C)C[C@H](N)[C@@H](O)C[C@H](C(NCC(C([2H])([2H])[2H])(C([2H])([2H])[2H])C(N)=O)=O)C(C)C)C=C1.OC(/C=C/C(O)=O)=O.COC2=C(OCCCOC)C=C(C[C@H](C(C)C)C[C@H](N)[C@@H](O)C[C@H](C(NCC(C([2H])([2H])[2H])(C([2H])([2H])[2H])C(N)=O)=O)C(C)C)C=C2 | ||
| 分子式 | C30H47D6N3O6•1/2C4H4O4 | 分子量 | 615.8 |
| 溶解度 | DMSO: soluble,Methanol: 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.6239 mL | 8.1195 mL | 16.239 mL |
| 5 mM | 0.3248 mL | 1.6239 mL | 3.2478 mL |
| 10 mM | 0.1624 mL | 0.812 mL | 1.6239 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。
[Aliskiren hemifumarate]
Dtsch Med Wochenschr 2008 Jun;133(24):1308-12.PMID:18465684DOI:10.1055/s-2008-1077232.
Aliskiren, a renin inhibitor, is the first in a new class of drugs interfering with the renin angiotensin system. Aliskiren was approved by the US Food and Drug Administration (FDA) in March 2007, and in Europe in August 2007 for the treatment of hypertension (marketed as Tekturna and Rasilez, respectively). Several clinical trials demonstrated effective blood pressure reduction due to aliskiren treatment. Whether aliskiren exhibits morbidity and mortality benefits for patients beyond its blood pressure reduction capability, can only be judged after realization of comparative long-term clinical trials. Furthermore, it remains to be seen, whether the use of aliskiren will be indicated for treatment of additional diseases, as it was the case for other inhibitors of the renin angiotensin system. In fact, recent and ongoing clinical trials regarding heart failure and diabetic nephropathy demonstrated first beneficial effects of aliskiren in these conditions (reduction of urinary albumin/creatinine-ratio and NTproBNP, respectively).
Aliskiren hemifumarate Proliposomes for Improved Oral Drug Delivery: Formulation Development, In Vitro and In Vivo Permeability Testing
Molecules 2022 Jul 28;27(15):4828.PMID:35956779DOI:10.3390/molecules27154828.
The objective of this study was to develop proliposomal formulations for a poorly bioavailable drug, aliskiren hemifumarate (AKH). A solvent evaporation method was used to prepare proliposomes using different lipids. The lipids of selection were soy phosphatidylcholine (SPC), dimyristoylphosphatidylcholine (DMPC), and dimyristoylphosphatidylglycerol sodium (DMPG Na), stearylamine, and cholesterol in various ratios. Proliposomes were evaluated for particle size, zeta potential, in vitro drug release, in vitro permeability, and in vivo pharmacokinetics upon hydration with aqueous phase. In vitro drug release studies were conducted in 0.01 N hydrochloric acid using USP type II dissolution apparatus. Parallel artificial membrane permeation assay (PAMPA) and Caco-2 cell line models were used to study the in vitro drug permeation. Male Sprague-Dawley (SD) rats were used to conduct in vivo pharmacokinetic studies. Among different formulations, proliposomes with drug/DMPC/cholesterol/stearylamine in the ratio of 1:5:0.025:0.050 (w/w/w/w) demonstrated the desired particle size, higher zeta potential, and higher encapsulation efficiency. The PAMPA and Caco-2 cell line experiments showed a significantly higher permeability of AKH with proliposomes as compared to pure AKH. In animal studies, the optimized formulation of proliposomes showed significant improvement in the rate and extent of absorption of AKH. Specifically, following a single oral administration, the relative bioavailability of AKH proliposome formulation was 230% when compared to pure AKH suspension.
Pharmacovigilance analysis of adverse event reports for aliskiren hemifumarate, a first-in-class direct renin inhibitor
Ther Clin Risk Manag 2011;7:337-44.PMID:21941439DOI:10.2147/TCRM.S23889.
Background: The purpose of this study was to examine the postmarketing safety profile of aliskiren hemifumarate, a first-in-class direct renin inhibitor. Methods: The US Adverse Event Reporting System (AERS) was utilized to conduct a retrospective pharmacovigilance analysis by applying the Multi-item Gamma Poisson Shrinker data mining algorithm to calculate empiric Bayes geometric mean (EBGM) values of aliskiren-related adverse event reports. Reports received from January 2007 through December 2008 are included in this analysis. Results: In total, 1592 reports for aliskiren are identified in the AERS. Aliskiren was associated with reports of angioedema (EBGM 3.9, 95% confidence interval [CI] 3.2-4.7) and renal dysfunction (EBGM 3.4, 95% CI 2.6-4.5). Reports of hyperkalemia, dry cough, and diarrhea were also linked to aliskiren (EBGM 7.4, 95% CI 3.4-13.0, EBGM 11.0, 95% CI 7.8-14.2, EBGM 4.3, 95% CI 3.2-5.8, respectively). Conclusion: Angioedema and renal dysfunction are potential adverse events associated with exposure to aliskiren. Patients with signs and symptoms of angioedema should stop aliskiren and seek urgent medical help. Aliskiren should not be used by patients with a risk of renal impairment. Additional studies are warranted to quantify further the risk of these events in patients with hypertension.
Simultaneous Determination of Aliskiren hemifumarate, Amlodipine Besylate and Hydrochlorothiazide in Spiked Human Plasma Using UPLC-MS/MS
J Chromatogr Sci 2015 Aug;53(7):1178-84.PMID:25575509DOI:10.1093/chromsci/bmu213.
A sensitive UPLC-MS/MS method was developed and validated for simultaneous estimation of aliskiren hemifumarate (ALS), amlodipine besylate (AML) and hydrochlorothiazide (HCZ) in spiked human plasma using valsartan as an internal standard (IS). Liquid-liquid extraction was used for purification and pre-concentration of analytes. The mobile phase consisted of 0.1% formic acid in ammonium acetate buffer (0.02 M, pH 3.5) and methanol (25:75, v/v), flowing through XBridge BEH (50 × 2.1 mm ID, 5 µm) C18 column, at a flow rate of 0.6 mL min(-1). Multiple reaction monitoring (MRM) transitions were measured using an electrospray source in the positive ion mode for ALS and AML, whereas HCZ and IS were measured in negative ion mode. Validation of the method was performed as per US-FDA guidelines with linearity in the range of 2.0-400.0, 0.3-25.0 and 5.0-400.0 ng mL(-1) for ALS, AML and HCZ, respectively. In human plasma, ALS, AML and HCZ were stable for at least 1 month at -70 ± 5°C and for at least 6 h at ambient temperature. After extraction from plasma, the reconstituted samples of ALS, AML and HCZ were stable in the autosampler at ambient temperature for 6 h. The LC-MS/MS method is suitable for bioequivalence and pharmacokinetic studies of this combination.
A validated LC method for the determination of the enantiomeric purity of aliskiren hemifumarate in bulk drug samples
J Chromatogr Sci 2012 Oct;50(9):799-802.PMID:22732253DOI:10.1093/chromsci/bms073.
High-performance liquid chromatography enantioseparation of aliskiren hemifumarate was accomplished on an immobilized-type Chiralpak IC chiral stationary phase under both polar organic and reversed-phase modes. A simple analytical method was developed and validated using a mixture of acetonitrile-n-butylamine 100:0.1 (v/v/) as a mobile phase with a flow rate maintained at 1.0 mL/min. Ultraviolet detection was carried out at 228 nm. Resolution between the two enantiomers was greater than 3.0. This method was capable of detecting the R-isomer to a level of 0.2 μg/mL. The method was validated as per International Conference on Harmonization guidelines and found to be robust. The method is very useful for routine evaluation of the quality of aliskiren hemifumarate in bulk drug manufacturing units.