HPLC detection method for Cangrelor intermediate impurities
A 0.14% na3po4, gland technology, applied in measuring devices, instruments, scientific instruments, etc., can solve the problems of no resolution HPLC detection method, weak reversed-phase chromatography retention, poor solubility, etc., to avoid retention time drift, avoid Bimodal phenomenon, highly specific effect
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Publication Date
- 2021-04-09
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Abstract
Description
technical field
[0001] The invention belongs to the field of pharmaceutical preparations, and in particular relates to an HPLC detection method for Cangrelor intermediate impurities. Background technique
[0002] Impurities introduced in pharmaceutical processes are often referred to as related substances. The inspection of drug-related impurity items needs to be clearly targeted. The impurity inspection items in the drug standards should include the impurities and degradation products that are detected in the quality research and stability inspection of the drug and appear in the batch production. Cangrelor is a short-acting reversible inhibitor of platelet P2Y12, which is mainly used to prevent coronary artery plunger caused by blood clotting in adult patients during percutaneous coronary intervention (PCI). On June 22, 2016, the U.S. FDA approved Cangrelor, an anti-platelet drug injection from Medicine Company.
[0003]
[0004] The synthesis method of cangrelor is ...
Examples
Embodiment 1
[0049]
[0050] In a 500ml reaction flask, add 10g of 5-amino-1-β-D-ribofuranosyl imidazole-4-carboxamide oxime hydrochloride to 200ml of methanol water (8:1) solution, add sodium hydroxide to adjust the pH to 9- 10, and 50ml of carbon disulfide was added, reacted at 130°C for 7h under high pressure, cooled to room temperature, and concentrated to obtain a crude product, the content of adenosine-2-thione was 75.27% as determined by HPLC (see Example 2 for the analysis method). The impurity compound disulfide was separated by column chromatography.
[0051] 1 HNMR(400MHz,DMSO-d6):δ8.28(s,2H),7.55(s,4H),5.81(d,J=6.0Hz,2H),5.43(d,J=6.1Hz,2H),5.16 (d, J=4.9Hz, 2H), 4.95(t, J=5.6Hz, 2H), 4.56(q, J=5.7Hz, 2H), 4.12(q, J=4.4Hz, 2H), 3.90(q ,J=4.1Hz,2H),3.55(ddt,J=49.3,11.9,4.9Hz,4H).
[0052] 13 CNMR(101MHz,DMSO-d6):δ161.92,156.27,150.77,139.67,118.15,87.51,86.08,73.89,70.99,62.05,39.95.
[0053] HRMS(ESI)m / z Found:597.1300 Calcd.:C 20 h 24 N 10 o 8 S 2 :(M+H) + 597.1298....
Embodiment 2
[0055] Instrument model: high performance liquid chromatography (Thermo U3000 equipped with DAD detector, the United States); analytical balance (SartoriusBSA224S, Sartorius Scientific Instruments (Beijing) Co., Ltd.); ultrasonic cleaner (KQ100DE type, Kunshan Ultrasonic Instrument Co., Ltd.) .
[0056] Substituting purine and disulfide reference substances, through NMR, mass spectrometry, chromatography, organic solvent residues, and moisture content determination, it was calibrated as content> 99.0%, single impurity<0.2%; methanol was chromatographically pure grade; pure water was measured by a pure water meter ( Milli-QDirect8, Millipore, France), other reagents were of analytical grade.
[0057] 1. Content detection of substituted purines and disulfides in samples
[0058] A. Prepare the test product
[0059] Accurately weigh 150 mg of the adenosine-2-thione test product prepared in Example 1, and dissolve it in 2mLDMSO with the assistance of ultrasound to prepare an ini...