6-O-desmethyl Donepezil
(Synonyms: 6-O-去甲基多奈哌齐) 目录号 : GC42584
An active metabolite of donepezil
Cas No.:120013-56-1
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
6-O-desmethyl Donepezil is an active metabolite of the acetylcholinesterase inhibitor donepezil . It is formed through dealkylation by the cytochrome P450 (CYP) isoform CYP2D6. It inhibits human ether a go-go (hERG) channels (IC50 = 1.5 µM in HEK293 cells expressing hERG).
| Cas No. | 120013-56-1 | SDF | |
| 别名 | 6-O-去甲基多奈哌齐 | ||
| Canonical SMILES | O=C1C(CC2CCN(CC3=CC=CC=C3)CC2)CC4=CC(OC)=C(O)C=C41 | ||
| 分子式 | C23H27NO3 | 分子量 | 365.5 |
| 溶解度 | Chloroform: soluble,Methanol: soluble | 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 | 2.736 mL | 13.6799 mL | 27.3598 mL |
| 5 mM | 0.5472 mL | 2.736 mL | 5.472 mL |
| 10 mM | 0.2736 mL | 1.368 mL | 2.736 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。
Simultaneous determination of donepezil, 6-O-desmethyl Donepezil and spinosin in beagle dog plasma using liquid chromatography‒tandem mass spectrometry and its application to a drug-drug interaction study
J Pharm Biomed Anal 2020 Jan 30;178:112919.PMID:31654856DOI:10.1016/j.jpba.2019.112919.
Spinosin, which is traditionally used for sedation and sleep disorders, has recently shown potential effects in alleviating memory loss. As spinosin is the main bioactive component in a standardized dried 50% ethanol extract of the seeds of Zizyphus jujuba var. spinosa, a Phase IIb clinical trial is ongoing, in Korea for the combination of the above extract formulated in a tablet (DHP1401 tablet) with donepezil hydrochloride (Aricept® tablet) in patients with mild to moderate Alzheimer's disease. Therefore, to promote safety and efficacy evaluations, a reliable method for the simultaneous detection and analysis of the two drugs is needed. Toward this end, in this study, we established and validated a rapid and sensitive LC-MS/MS method for the simultaneous determination of donepezil, its pharmacologically active metabolite 6-O-desmethyl Donepezil, and spinosin in beagle dog plasma (50 μL). After optimization of the system, we used methanol for simple protein precipitation. Chromatographic separation was performed using a Phenomenex Luna C18 column (100 × 2.0 mm, 3 μm) with a mobile phase consisting of 0.1% formic acid in acetonitrile-0.1% formic acid in distilled water (2:8, v/v) at a flow rate of 0.65 mL/min. All analytes were detected and quantified in selected reaction monitoring mode. All calibration curves showed good linearity (r ≥ 0.9965) over the concentration range of 0.02-20, 0.02-10, and 0.5-250 ng/mL for donepezil, for 6-O-desmethyl Donepezil, and spinosin, respectively. This validated method was then successfully applied to a pharmacokinetic study in beagle dogs with no evidence for potential drug-drug interactions between DHP1401 and donepezil hydrochloride. This information and optimized assay can be useful for the anticipated co-administration of these two drugs in clinical settings.
Chiral HPLC analysis of donepezil, 5-O-desmethyl donepezil and 6-O-desmethyl Donepezil in culture medium: application to fungal biotransformation studies
Anal Bioanal Chem 2012 Jul;404(1):257-66.PMID:22644152DOI:10.1007/s00216-012-6107-3.
An high performance liquid chromatography (HPLC) method for the enantioselective determination of donepezil (DPZ), 5-O-desmethyl donepezil (5-ODD), and 6-O-desmethyl Donepezil (6-ODD) in Czapek culture medium to be applied to biotransformation studies with fungi is described for the first time. The HPLC analysis was carried out using a Chiralpak AD-H column with hexane/ethanol/methanol (75:20:5, v/v/v) plus 0.3 % triethylamine as mobile phase and UV detection at 270 nm. Sample preparation was carried out by liquid-liquid extraction using ethyl acetate as extractor solvent. The method was linear over the concentration range of 100-10,000 ng mL(-1) for each enantiomer of DPZ (r ≥ 0.9985) and of 100-5,000 ng mL(-1) for each enantiomer of 5-ODD (r ≥ 0.9977) and 6-ODD (r ≥ 0.9951). Within-day and between-day precision and accuracy evaluated by relative standard deviations and relative errors, respectively, were lower than 15 % for all analytes. The validated method was used to assess DPZ biotransformation by the fungi Beauveria bassiana American Type Culture Collection (ATCC) 7159 and Cunninghamella elegans ATCC 10028B. Using the fungus B. bassiana ATCC 7159, a predominant formation of (R)-5-ODD was observed while for the fungus C. elegans ATCC 10028B, DPZ was biotransformed to (R)-6-ODD with an enantiomeric excess of 100 %.
Quantitation of donepezil and its active metabolite 6-O-desmethyl Donepezil in human plasma by a selective and sensitive liquid chromatography-tandem mass spectrometric method
Anal Chim Acta 2008 Nov 23;629(1-2):145-57.PMID:18940331DOI:10.1016/j.aca.2008.09.048.
A sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the simultaneous determination of donepezil (D) and its pharmacologically active metabolite, 6-O-desmethyl Donepezil (6-ODD) in human plasma is developed using galantamine as internal standard (IS). The analytes and IS were extracted from 500 microL aliquots of human plasma via solid-phase extraction (SPE) on Waters Oasis HLB cartridges. Chromatographic separation was achieved in a run time of 6.0 min on a Waters Novapak C18 (150 mm x 3.9 mm, 4 microm) column under isocratic conditions. Detection of analytes and IS was done by tandem mass spectrometry, operating in positive ion and multiple reaction monitoring (MRM) acquisition mode. The protonated precursor to product ion transitions monitored for D, 6-ODD and IS were at m/z 380.1-->91.2, 366.3-->91.3 and 288.2-->213.2, respectively. The method was fully validated for its selectivity, interference check, sensitivity, linearity, precision and accuracy, recovery, matrix effect, ion suppression/enhancement, cross-specificity, stability and dilution integrity. A linear dynamic range of 0.10-50.0 ng mL(-1) for D and 0.02-10.0 ng mL(-1) for 6-ODD was evaluated with mean correlation coefficient (r) of 0.9975 and 0.9985, respectively. The intra-batch and inter-batch precision (%CV, coefficient of variation) across five quality control levels was less than 7.5% for both the analytes. The method was successfully applied to a bioequivalence study of 10mg donepezil tablet formulation in 24 healthy Indian male subjects under fasting condition.
A rapid and sensitive LC-MS/MS method for quantification of donepezil and its active metabolite, 6-O-desmethyl Donepezil in human plasma and its pharmacokinetic application
Biomed Chromatogr 2011 Aug;25(8):943-51.PMID:21154884DOI:10.1002/bmc.1552.
A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method has been developed and fully validated for simultaneous quantification of donepezil and its active metabolite, 6-O-desmethyl Donepezil in human plasma. Analytes and the internal standard were extracted from human plasma by liquid-liquid extraction technique using a 30:70 v/v mixture of ethyl acetate and n-hexane. The reconstituted samples were chromatographed on a C(18) column by using a 70:30 v/v mixture of acetonitrile and ammonium formate (5 mm, pH 5.0) as the mobile phase at a flow rate of 0.6 mL/min. The calibration curve obtained was linear (r ≥ 0.99) over the concentration range of 0.09-24.2 ng/mL for donepezil and 0.03-8.13 ng/mL for 6-O-desmethyl Donepezil. The results of the intra-day and inter-day precision and accuracy studies were well within the acceptable limits. The proposed method was successfully applied for the estimation of the drug in real time plasma samples for pharmacokinetic studies.
Impact of Plasma Donepezil Concentration on Behavioral and Psychological Symptoms of Dementia in Patients with Alzheimer's Disease
Dement Geriatr Cogn Dis Extra 2021 Dec 2;11(3):264-272.PMID:35082823DOI:10.1159/000516938.
Background/aims: The behavioral and psychological symptoms of dementia (BPSD) detract from the quality of life of not only dementia patients but also their family members and caregivers. Donepezil is used to treat Alzheimer's disease and is metabolized via cytochrome P450 (CYP) 2D6 and CYP3A4/5. It is controversial whether donepezil improves or exacerbates BPSD. This study investigated the relationships among BPSD, the pharmacokinetics of donepezil including its metabolite, 6-O-desmethyl Donepezil, genetic polymorphisms of CYPs and P-glycoprotein, and patient backgrounds in 52 patients with Alzheimer's disease. Methods: BPSD were assessed using the Neuropsychiatric Inventory (NPI), with scores ≥20 points defined as severe BPSD. Plasma donepezil and 6-O-desmethyl Donepezil concentrations were measured using liquid chromatography-tandem mass spectrometry. Results: Although significant relationships between NPI scores and plasma donepezil concentrations were not seen, none of the 15 patients (29%) with high plasma donepezil concentrations (≥60 ng/mL) developed severe BPSD. Polymorphisms of CYP2D6, CYP3A5, and ABCB1 did not influence NPI scores. There were no significant relationships between NPI and patient background factors such as dosing regimen, concomitant use of other drugs, or laboratory test results. Two patients who underwent multiple blood samplings over 2 years showed an inverse correlation between plasma donepezil concentrations and NPI scores. Discussion/conclusions: These results indicate that higher plasma concentrations of donepezil contribute to preventing or alleviating rather than developing or deteriorating BPSD.