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Method for detecting three potential genotoxic impurities in meropenem

A genotoxicity and detection method technology, applied in the direction of measuring devices, instruments, scientific instruments, etc., can solve the problems affecting the detection of genotoxic impurities, low limit of genotoxic impurities, large background interference, etc., to achieve strong operability and specificity , high sensitivity, and the effect of ensuring quality controllability

Pending Publication Date: 2022-04-12
深圳华药南方制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The maximum daily dosage of meropenem is large, and the limit of genotoxic impurities is low. In general HPLC analysis methods, the background interference of meropenem is relatively large, which affects the detection of genotoxic impurities

Method used

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  • Method for detecting three potential genotoxic impurities in meropenem
  • Method for detecting three potential genotoxic impurities in meropenem
  • Method for detecting three potential genotoxic impurities in meropenem

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] Instrument: Shimadzu LC-20AT high performance liquid chromatography (SIL-20A autosampler, CTO-10AS constant temperature column thermostat, SPD-20A ultraviolet detector);

[0036] Chromatographic column: YMC-Pack Pro C18 chromatographic column (4.6mm×150mm, 3μm);

[0037] Mobile phase: use 0.2% potassium dihydrogen phosphate buffer solution (adjust pH 3.0 with phosphoric acid)-methanol (50:50) as the mobile phase, and use isocratic elution for separation;

[0038] Detector: UV detector, dual wavelength detection mode, the detection wavelengths are 230nm and 285nm respectively;

[0039] Flow rate: 1.0ml / min, injection volume: 50μl, column temperature: 40℃;

[0040] Sample solution preparation diluent: water;

[0041] Impurity localization solution: Take the appropriate amount of the reference substances of impurities 1, 2, and 3, dissolve and dilute them with diluent respectively to make a solution containing 100 μg of each impurity in each 1ml, shake well, and obtain; ...

Embodiment 2

[0046] Instrument: Shimadzu LC-20AT high performance liquid chromatography (SIL-20A autosampler, CTO-10AS constant temperature column thermostat, SPD-20A ultraviolet detector);

[0047] Chromatographic column: Thermo BDS C18 chromatographic column (4.6mm×150mm, 3μm);

[0048] Mobile phase: use 0.4% potassium dihydrogen phosphate buffer solution (adjust pH 4.0 with phosphoric acid)-methanol (55:45) as the mobile phase, and use isocratic elution for separation;

[0049] Detector: UV detector, dual wavelength detection mode, the detection wavelengths are 230nm and 285nm respectively;

[0050] Flow rate: 1.2ml / min, injection volume: 50μl, column temperature: 35°C;

[0051] Sample solution preparation diluent: water;

[0052] System suitability solution: take the appropriate amount of the reference substances of impurities 1, 2, and 3, weigh them accurately, dissolve and dilute them with diluent to make a mixed solution containing 0.1 μg of each impurity in each 1ml, shake well, an...

Embodiment 3

[0055] Embodiment 3 detection limit test

[0056] Take an appropriate amount of impurities 1, 2, and 3, weigh them accurately, dissolve them with water and dilute them into solutions of a series of concentrations, inject samples for determination, take the concentration point with a signal-to-noise ratio ≥ 3 as the detection limit, and the result is:

[0057] The detection limits of impurity 1, impurity 2, and impurity 3 are 1.6ppb, 1.6ppb, and 3.2ppb respectively, and the detection limits of each impurity are below the concentration of 0.000005% of the main component, meeting the sensitivity requirements of impurity inspection.

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Abstract

The invention relates to a method for detecting three potential genotoxic impurities in meropenem, and belongs to the technical field of pharmaceutical analysis, the potential genotoxic impurities comprise 4-nitrotoluene, p-methylaniline and 4-nitrobenzyl alcohol; high performance liquid chromatography is adopted, and chromatographic conditions are as follows: an octadecyl silica gel chromatographic column; carrying out isocratic elution by taking a monopotassium phosphate buffer solution and methanol as mobile phases; the ultraviolet detector adopts a dual-wavelength mode; the flow rate is 0.5-2.0 ml / min, the sample injection volume is 10-100 microliters, and the column temperature is 20-50 DEG C; during determination, a system applicability solution, an impurity positioning solution and a test solution are respectively injected into a high performance liquid chromatograph, and chromatograms are recorded. According to the method, three genotoxic impurities in meropenem are controlled at the same time through the high performance liquid chromatography, complete separation of all the impurities is achieved, operability and specificity are high, and high sensitivity, accuracy and precision are achieved.

Description

technical field [0001] The invention relates to a method for detecting three potential genotoxic impurities in meropenem, belonging to the technical field of drug analysis. Background technique [0002] Meropenem is a synthetic broad-spectrum carbapenem antibiotic that produces antibacterial effects mainly by inhibiting the synthesis of bacterial cell walls, and easily penetrates the cell walls of most Gram-positive and negative bacteria to reach its target penicillin-binding protein (PBPs). [0003] Analysis of the raw materials and production processes used in the production of meropenem revealed that there were three potential genotoxic impurities, 4-nitrotoluene, p-methylaniline, and 4-nitrobenzyl alcohol, and the above three genotoxic impurities contained The genotoxic impurity warning structure is potentially destructive to DNA, and long-term use may cause cancer. Therefore, strict control of genetic impurities in the product is required. However, the above three gen...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02
CPCY02A50/30
Inventor 王立忱黄世青于会贤王召朋贾欣秒王伶贾立李庆磊
Owner 深圳华药南方制药有限公司
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