Perindoprilat
(Synonyms: 培哚普利,S-9780) 目录号 : GC44599An active ACE inhibitor
Cas No.:95153-31-4
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
Perindoprilat is the active metabolite of perindopril, an inhibitor of angiotensin converting enzyme (ACE) that has efficacy against hypertension. [1] Perindoprilat specifically and competitively inhibits ACE in vitro with IC50 values ranging between 1.5 and 3.2 nM. Elimination of perindoprilat is decreased in the elderly and in patients with heart or renal failure.[1][2][3]
Reference:
[1]. Wang, J.g., Pimenta, E., and Chwallek, F. Comparative review of the blood pressure-lowering and cardiovascular benefits of telmisartan and perindopril. Vascular Health and Risk Management 10, 189-200 (2014).
[2]. Sennesael, J., Ali, A., Sweny, P., et al. The pharmacokinetics of perindopril and its effects of serum angiotensin converting enzyme activity in hypertensive patients with chronic renal failure. Br.J.Clin.Pharmac. 33, 93-99 (1992).
[3]. Parker, E., Aarons, L., Rowland, M., et al. The pharmacokinetics of perindoprilat in normal volunteers and patients: Influence of age and disease state. European Journal of Pharmaceutical Sciences 26(1), 104-113 (2005).
| Cas No. | 95153-31-4 | SDF | |
| 别名 | 培哚普利,S-9780 | ||
| 化学名 | (2S,3aS,7aS)-1-[(2S)-2-[[(1S)-1-carboxybutyl]amino]-1-oxopropyl]octahydro-1H-indole-2-carboxylic acid | ||
| Canonical SMILES | [H][C@]12[C@](N(C([C@H](C)N[C@@H](CCC)C(O)=O)=O)[C@H](C(O)=O)C2)([H])CCCC1 | ||
| 分子式 | C17H28N2O5 | 分子量 | 340.4 |
| 溶解度 | DMF: 30 mg/ml,DMSO: 30 mg/ml,PBS (pH 7.2): 10 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 | 2.9377 mL | 14.6886 mL | 29.3772 mL |
| 5 mM | 0.5875 mL | 2.9377 mL | 5.8754 mL |
| 10 mM | 0.2938 mL | 1.4689 mL | 2.9377 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。
Perindoprilat monohydrate
Acta Crystallogr C 2012 Nov;68(Pt 11):o443-6.PMID:23124459DOI:10.1107/S0108270112041583.
The title compound [systematic name: (1S)-2-((S)-{1-[(2S,3aS,7aS)-2-carboxyoctahydro-1H-indol-1-yl]-1-oxopropan-2-yl}azaniumyl)pentanoate monohydrate], C(17)H(28)N(2)O(5)·H(2)O, (I)·H(2)O, the active metabolite of the antihypertensive and cardiovascular drug perindopril, was obtained during polymorphism screening of Perindoprilat. It crystallizes in the chiral orthorhombic space group P2(1)2(1)2(1), the same as the previously reported ethanol disolvate [Pascard, Guilhem, Vincent, Remond, Portevin & Laubie (1991). J. Med. Chem. 34, 663-669] and dimethyl sulfoxide hemisolvate [Bojarska, Maniukiewicz, Sieroń, Fruziński, Kopczacki, Walczyński & Remko (2012). Acta Cryst. C68, o341-o343]. The asymmetric unit of (I)·H(2)O contains one independent Perindoprilat zwitterion and one water molecule. These interact via strong hydrogen bonds to give a cyclic R(2)(2)(7) synthon, which provides a rigid molecular conformation. The geometric parameters of all three forms are similar. The conformations of the perhydroindole group are almost identical, but the n-alkyl chain has conformational freedom. A three-dimensional hydrogen-bonding network of O-H···O and N-H···O interactions is observed in the crystal structure of (I)·H(2)O, similar to the other two solvates, but because of the presence of different solvents the three crystal structures have diverse packing motifs. All three solvatomorphs are additionally stabilized by nonclassical weak C-H···O contacts.
Perindoprilat changes ANG (1-9) production in renal arteries isolated from young spontaneously hypertensive rats after ANG I incubation
Physiol Res 2016 Nov 8;65(4):561-570.PMID:26988149DOI:10.33549/physiolres.933015.
We used mass spectrometry to quantitate production of angiotensinogen metabolites in renal artery of 3- and 7-month-old Wistar-Kyoto (WKY) and Spontaneously Hypertensive Rats (SHR). Tissue fragments were incubated for 15 min in oxygenated buffer, with added angiotensin I. Concentrations of angiotensins I (ANG I), II (ANG II), III (ANG III), IV (ANG IV), angiotensin (1-9) [ANG (1-9)], angiotensin (1-7) [ANG (1-7)], and angiotensin (1-5) [ANG (1-5)], excreted into the buffer during experiment, were measured using liquid chromatography-mass spectrometry (LC/MS) and expressed per mg of dry tissue. Effects of pretreatment with 10 microM Perindoprilat on the production of ANG I metabolites were quantitated. Background production of any of ANG I metabolites differed neither between WKY and SHR rats nor between 3- and 7-month-old rats. Perindoprilat pretreatment of renal arteries resulted, as expected, in decrease of ANG II production. However, renal arteries of 7-month-old SHR rats were resistant to ACE inhibitor and did not change ANG II production in response to Perindoprilat. In renal arteries, taken from 3-month-old rats, pretreated with Perindoprilat, incubation with ANG I, resulted in the level of ANG (1-9) significantly higher in SHR than WKY rats. Our conclusion is that in SHR rats, sensitivity of renal artery ACE to Perindoprilat inhibition changes with age.
A UPLC-MS/MS method for quantification of perindopril and Perindoprilat and applied in a bioequivalence study for their pharmacokinetic parameter measurement
Int J Clin Pharmacol Ther 2020 Feb;58(2):103-111.PMID:31845865DOI:10.5414/CP203593.
Objectives: To investigate the pharmacokinetic parameters of perindopril and Perindoprilat in healthy volunteers, a simple and sensitive UPLC-MS/MS method with isotope-labeled internal standards of perindopril-d4 and perindoprilat-d4 was established and further applied in a bioequivalence study. Materials and methods: A simple and sensitive UPLC-MS/MS method with isotope-labeled internal standards of perindopril-d4 and perindoprilat-d4 was validated and applied in a single-center, randomized, cross-over, and two-period bioequivalence study. 20 healthy Chinese subjects (16 males and 4 females) were enrolled and had their plasma concentrations of perindopril and Perindoprilat quantified and calculated for the pharmacokinetic parameters. After acetonitrile precipitation, the analytes and internal standards were gradient eluted with methanol-acetonitrile-ammonium acetate on an Acquity UPLC BEH C18 (2.1 × 50 mm, 1.7 µm) column. Detection was carried out in a multireaction monitoring mode using positive ionization electrospray mass spectrometry. Results: The total chromatographic run time was 4 minutes with retention time for perindopril and perindopril-d4 of ~ 1.86 minutes, whereas Perindoprilat and perindoprilat-d4 was ~ 1.79 minutes. The calibration curves of perindopril and Perindoprilat were linear over 0.4 - 80 ng/mL and 0.2 - 40 ng/mL, respectively. The method was fully validated to meet the requirement for bioassay in accuracy (89.6 - 112.4%), precision (coefficient of variation (CV) ≤ 13.8%), recovery (79.65 - 97.83%), matrix effect (CV ≤ 5.9%), and stability (CV ≤ 10.0%). The 90% confidence intervals (CIs) for the geometric mean ratios of Cmax, AUC0-tlast, and AUC0-∞ of perindopril and Perindoprilat all fell within the bioequivalence acceptance criteria (80 - 125%). There were no significant differences between the two formulations in terms of tmax and T1/2 of perindopril and Perindoprilat. There was no adverse event in this clinical study. Interestingly, it was found that the pharmacokinetics of Perindoprilat in 1 subject were significantly different from that of the others which may be associated with genetic diversity. Conclusion: This method was successfully applied to the bioequivalence test of two perindopril tert-butylamine tablets. The two one-sided t-tests showed that these two products were bioequivalent.
Simultaneous determination of indapamide, perindopril and its active metabolite Perindoprilat in human plasma using UPLC-MS/MS method
J Chromatogr B Analyt Technol Biomed Life Sci 2021 Apr 15;1169:122585.PMID:33706186DOI:10.1016/j.jchromb.2021.122585.
Lots of studies showed the combination therapy of perindopril, indapamide and amlodipine could increase BP lowering efficacy and the benefits of high-risk patients. To evaluate potential pharmacokinetic interaction, a simultaneous UPLC-MS/MS quantification method of perindopril, Perindoprilat and indapamide in human plasma was developed and validated. The plasma samples were prepared by solid phase extraction, and then separated on an X-terra MS C18 (2.1 mm × 150 mm, 3.5 μm) with isocratic elution. The ion transitions at m/z 369.165 → 172.000 (perindopril), m/z 341.146 → 170.112 (Perindoprilat), m/z 366.010 → 132.100 (indapamide), m/z 389.120 → 206.200 (S10211-1, IS1) and m/z 394.080 → 160.200 (S1641, IS2) were monitored under the positive ion mode of electrospray ionization with multiple reaction monitoring. This method exhibited great sensitivity, linearity, accuracy, and precision for the determination of perindopril, Perindoprilat and indapamide over the range of 0.250-50.0 ng/mL. The average extraction recovery of perindopril, Perindoprilat and indapamide samples at low, medium, and high concentration levels were between 85.9% and 93.6%, respectively. The stability of analytes over different storage and processing conditions in the whole study was also validated. The method is fast, accurate, sensitive and reproducible, which is suitable for the detection of the concentration of perindopril, Perindoprilat and indapamide in human plasma.
The effect of haemodialysis on the pharmacokinetics of Perindoprilat after long-term perindopril
Eur J Clin Pharmacol 1993;44(2):183-7.PMID:8453964DOI:10.1007/BF00315478.
We have studied the pharmacokinetics of Perindoprilat, the active metabolite of perindopril, in 7 hypertensive patients undergoing haemodialysis after short-term and long-term (1 month) perindopril. We also measured angiotensin-converting enzyme activity. Each subject took 2 mg of perindopril after a 4-hour haemodialysis. Serial blood samples were obtained each hour during dialysis and between dialysis (7 samples over 44 h). Perindoprilat steady state was reached within 5 haemodialysis sessions. There was a high degree of angiotensin converting enzyme inhibition after the first dose. Administration for 1 month did not modify the time to peak Perindoprilat concentration but significantly increased the mean maximal concentration: 10.2 versus 26.8 ng.ml-1. The mean accumulation ratio was 3.5. The mean reduction in Perindoprilat concentration after dialysis was greater than 50%. Perindoprilat haemodialysis clearance was 62 ml.min-1 after the first administration and 72 ml.min-1 after 1 month. Tolerance of perindopril was good throughout the study. Treatment can be begun with 2 mg of perindopril after haemodialysis in hypertensive patients undergoing haemodialysis.