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HPLC detection method of cangrelor related substances

A detection method and technology of detection conditions, applied in measurement devices, instruments, scientific instruments, etc., can solve the problems of affecting the active site of the stationary phase, failing to achieve separation effect, long elution separation time, etc., and achieving a simple and fast analysis method. , Improve drug safety, the effect of accurate quantitative measurement results

Active Publication Date: 2019-05-21
CSPC ZHONGQI PHARM TECH (SHIJIAZHUANG) CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In June 2015, the FDA approved Madison Pharmaceuticals’ anti-platelet injection cangrelor (trade name Kengreal) as a second-line drug, but no domestic manufacturer has been approved for marketing
Adenosine triphosphate is an unstable substance, which is easily affected by factors such as moisture and temperature. It takes off the phosphate bond to generate adenosine diphosphate (ADP) and adenosine monophosphate (AMP), which affects the quality of the preparation.
[0011] However, the inventors of the present invention have found that applying the above-mentioned detection method to the detection of cangrelor-related substances has the following disadvantages: (1) the main component peak is delayed; (2) the buffer salt concentration is 0.2mol / L, and the high-concentration salt More crystals will be precipitated in the high-pressure mobile phase, resulting in damage to the chromatographic column and the pump head structure; (3) 0.005mol / L of tetrabutylammonium bromide is added, which is an alkaline ion-pairing reagent, which is compatible with the fixed The combination produces irreversible adsorption, which affects the active sites of the stationary phase and causes irreversible damage to the chromatographic column
The inventors of the present invention applied the above detection method to the detection of cangrelor-related substances, and the results showed that the detection method could not achieve the expected separation effect, and the elution and separation time was long

Method used

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  • HPLC detection method of cangrelor related substances

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1: Detection of related substances of cangrelor

[0049] Instruments and equipment: high performance liquid chromatography: Agilent 1260 high performance liquid chromatography, chromatographic column: WatersSymmetry C18 (4.6mm × 250mm, 5μm).

[0050] Chromatographic conditions: mobile phase: mobile phase A: 15mmol L -1 Diammonium hydrogen phosphate sodium perchlorate solution (take 1.98g of diammonium hydrogen phosphate and 2.11g of sodium perchlorate, add purified water to dilute to 1000mL, adjust pH to 7.0 with phosphoric acid); mobile phase B: acetonitrile, use gradient elution . Detection wavelength: 242nm, column temperature: 30°C; injection volume: 20μL; flow rate: 1.0mL min -1 .

[0051] The specific gradient elution process is as follows:

[0052]

[0053]

[0054] Experimental method: Take 1 part of the mixed solution to be used for sample analysis under the above-mentioned chromatographic conditions, and record the chromatogram (see figure ...

Embodiment 2

[0056] Example 2: Detection of related substances of cangrelor

[0057] Instruments and equipment: high performance liquid chromatography: Agilent 1260 high performance liquid chromatography, chromatographic column: WatersSymmetry C18 (4.6mm × 250mm, 5μm).

[0058] Chromatographic conditions: mobile phase: mobile phase A: 15mmol L -1 Dipotassium hydrogen phosphate sodium perchlorate solution (take 3.42g of dipotassium hydrogen phosphate and 2.11g of sodium perchlorate, add purified water to dilute to 1000mL, adjust pH to 7.0 with phosphoric acid); mobile phase B: acetonitrile, using gradient elution . Detection wavelength: 242nm, column temperature: 30°C; injection volume: 20μL; flow rate: 1.0mL min -1 .

[0059] The specific gradient elution process is as follows:

[0060]

[0061] Experimental method: Take 1 portion of the mixed solution to be used for sample analysis under the above-mentioned chromatographic conditions, and record the chromatogram.

[0062] Experime...

Embodiment 3

[0063] Example 3: Detection of related substances of cangrelor

[0064] Instruments and equipment: high performance liquid chromatography: Agilent 1260 high performance liquid chromatography, chromatographic column: CAPCELLPAK C18 (4.6mm×250mm, 5μm).

[0065] Chromatographic conditions: mobile phase: mobile phase A: 15mmol L -1 Diammonium hydrogen phosphate sodium perchlorate solution (take 1.98g of diammonium hydrogen phosphate and 2.11g of sodium perchlorate, add purified water to dilute to 1000mL, adjust pH to 7.0 with phosphoric acid); mobile phase B: acetonitrile, use gradient elution . Detection wavelength: 242nm, column temperature: 30°C; injection volume: 20μL; flow rate: 1.0mL min -1 .

[0066] The specific gradient elution process is as in Example 1.

[0067] Experimental method: Take 1 portion of the mixed solution to be used for sample analysis under the above-mentioned chromatographic conditions, and record the chromatogram.

[0068] Experimental results: eac...

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Abstract

The invention provides a high performance liquid chromatography detection method of a cangrelor related substance. The method comprises the following steps: adopting a reversed-phase chromatographic column; the filler being octadecyl bonded silica gel; and carrying out gradient elution by taking a phosphate sodium perchlorate buffer solution as a mobile phase A and acetonitrile as a mobile phase B. The method has the advantages of strong specificity, high sensitivity and accurate quantitative determination result; the analysis method is simple, convenient and rapid, can better separate all impurities in a short time, has a separation degree between each chromatographic peak of more than 1.5, can comprehensively detect the cangrelor related substance and the cangrelor related substance in the preparation of the cangrelor, improves the safety of the medicine, and provides a basis for formulating the quality standards of the cangrelor bulk drug and the preparation of the cangrelor.

Description

technical field [0001] The invention relates to the field of drug analysis, in particular to a high-performance liquid chromatography detection method for cangrelor-related substances. Background technique [0002] Cangrelor was developed by AstraZeneca, and Madison Pharmaceuticals acquired the license to Cangrelor from AstraZeneca in December 2003. In June 2015, the FDA approved Madison Pharmaceuticals' anti-platelet injection cangrelor (trade name Kengreal) as a second-line drug, but no domestic manufacturer has been approved for marketing. [0003] Cangrelor is a non-thienopyridine purinoceptor P2Y 12 The antagonist comes from the structural modification of the ATP molecule, replacing the anhydride group with a methylene group and a halogen, so that the half-life is prolonged and the antagonistic activity is improved. Phase II clinical research shows that cangrelor has stronger anti-platelet aggregation effect than clopidogrel, and has good safety [2] . It can be used...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/89G01N30/34
CPCY02A50/30
Inventor 陈玉洁王群梁鑫磊孙开莉蒋明阳刘春玲吕健
Owner CSPC ZHONGQI PHARM TECH (SHIJIAZHUANG) CO LTD
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