High-performance liquid chromatography separation and determination method for related impurities in fosfomycin trometamol raw material drug and preparations thereof and application thereof

A technology of fosfomycin tromethamine and high performance liquid chromatography, which is applied in the field of medicine, can solve the problems affecting the impurity composition of fosfomycin tromethamine preparations, lack of structure confirmation and detection, and high detection cost, and achieve separation The detection method is simple and easy, the retention time changes greatly, and the effect of overcoming the rapid loss

Active Publication Date: 2019-11-01
SHANXI C&Y PHARMACEUTICAL GROUP CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

At the same time, due to the difference in formulation prescriptions, different excipients will also affect the impurity composition of fosfomycin trometamol formulations, especially the types of impurities that affect degradation, but there are no research reports on the structure confirmation and detection of these impurities.
[0012] After a large number of literature and patent searches, it can be seen that although capillary electrophoresis and electrospray ion trap mass spectrometry are useful in the prior art to detect related substances of fosfomycin trometamol, these two methods are due to the availability of detection equipment. However, the versatility is poor and the detection cost is high, so it has not been widely used.

Method used

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  • High-performance liquid chromatography separation and determination method for related impurities in fosfomycin trometamol raw material drug and preparations thereof and application thereof
  • High-performance liquid chromatography separation and determination method for related impurities in fosfomycin trometamol raw material drug and preparations thereof and application thereof
  • High-performance liquid chromatography separation and determination method for related impurities in fosfomycin trometamol raw material drug and preparations thereof and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] (1) Chromatographic conditions:

[0068] Column: Agilent Zorbax NH 2 (5μm, 4.6mm×250mm)

[0069] Column temperature: 30°C

[0070] Mobile phase: 20mmol / L phosphate buffer (potassium dihydrogen phosphate)-methanol (70:30)

[0071] Flow rate: 1.0ml / min

[0072] Detection: differential detector, detection temperature: 35°C

[0073] Injection volume: 10μl

[0074] (2) Sample solution preparation:

[0075] System suitability solution: take 0.3g of fosfomycin trometamol (batch number: Y18011607), wet it with 10μl of water, heat at 80°C for 12 hours, add mobile phase to dissolve and dilute to 10ml, shake well, and use it as solution A; Take another 0.3g of this product, dissolve it with solution A and dilute to 2.5ml, as a system suitability solution.

[0076] Sample solution: before using the new system, get fosfomycin tromethamine granules (lot number: 342414) in an appropriate amount, accurately weighed, add mobile phase to dissolve and quantitatively dilute into abo...

Embodiment 2

[0085] (1) Chromatographic conditions:

[0086] Column: Osaka Soda Capcell Pak NH 2 (5μm, 4.6×250mm)

[0087] Column temperature: 40°C

[0088] Mobile phase: 80mmol / L phosphate buffer (dipotassium hydrogen phosphate)-methanol (75:25)

[0089] Flow rate: 0.8ml / min

[0090] Detection: differential detector, detection temperature: 50°C

[0091] Injection volume: 1μl

[0092] (2) Sample solution preparation:

[0093] System suitability solution: Take 0.3g of fosfomycin trometamol (batch number: Y18011607), moisten it with 60μl of water, heat at 60°C for 12 hours, add mobile phase to dissolve and dilute to 20ml, shake well, and use it as solution A; Take another 0.3g of this product, dissolve it with solution A and dilute to 5ml, as a system suitability solution.

[0094] Sample solution: just use the new system, get fosfomycin tromethamine granules (lot number: 342414) in an appropriate amount, accurately weighed, add mobile phase to dissolve and quantitatively dilute into ...

Embodiment 3

[0097] (1) Chromatographic conditions:

[0098] Column: Phenomenex Luna-NH 2 (5μm, 4.6×250mm)

[0099] Column temperature: 20°C

[0100] Mobile phase: 50mmol / L phosphate buffer (potassium phosphate)-methanol (50:50)

[0101] Flow rate: 1.2ml / min

[0102] Detection: differential detector, detection temperature: 15°C

[0103] Injection volume: 100μl

[0104] (2) Sample solution preparation:

[0105] System suitability solution: Take 0.3g of fosfomycin trometamol powder (batch number: 20150501), wet it with 300μl of water, heat at 40°C for 12 hours, add mobile phase to dissolve and dilute to 50ml, shake well, and use it as solution A ; Take another 0.3g of this product, dissolve it with solution A and dilute it to 10ml, as a system suitability solution.

[0106]Sample solution: before using the new system, get fosfomycin tromethamine powder (batch number: 20150501) in an appropriate amount, accurately weighed, add mobile phase to dissolve and quantitatively dilute into abo...

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Abstract

The invention discloses a high-performance liquid chromatography separation and determination method for impurities in a fosfomycin trometamol raw material drug and preparations thereof and an application thereof, aiming at separating the impurities. According to the method, the aminopropyl silane-bonded silica gel is used as a chromatographic column of a filler, a differential detector is used for detection; and a phosphate buffer solution and methanol-acetonitrile are mixed as a mobile phase; the method includes the following steps of: 1, preparation of a system suitability solution: wettinga raw material drug or a preparation with water, heating, and dissolving and diluting the raw material drug or the preparation by the mobile phase to obtain a solution A; dissolving and diluting theraw material drug or the preparation by using the solution A to obtain the system suitability solution; 2, preparation of a test solution: taking the raw material drug or the preparation, and adding the mobile phase for dissolving and dilution to obtain the set content of fosfomycin trometamol as the test solution; 3, preparation of a reference solution: diluting the test solution by using the mobile phase to obtain a solution containing fosfomycin trometamol equivalent to a mass concentration of 0.3-0.5% of the test solution as the reference solution; and 4, determination method: separately injecting the above three solutions into a liquid chromatograph, and calculating the content of each impurity in the raw material drug by using a principal component self-control method.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a method for separation and determination of drug-related substances and its application, in particular to a high-performance liquid chromatography method for separation and determination of related impurities in fosfomycin trometamol raw material medicine and its preparation and its application . Background technique [0002] Fosfomycin trometamol, the English name is Fosfomycin Trometamol, the chemical name is (1R,2S)-(1,2-epoxypropyl)phosphonic acid·2-amino-2-(hydroxymethyl)-1, 3-propanediol salt (1:1), the chemical formula is C 7 h 18 NO 7 P, the molecular weight is 259.20, the CAS number is 78964-85-9, and the structural formula is as follows: [0003] [0004] The indication of fosfomycin trometamol is the treatment of acute simple lower urinary tract infection caused by sensitive bacteria (such as: acute cystitis, acute exacerbation of chronic cystitis, acute urethra...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02
CPCG01N30/02
Inventor 赵树军茅仁刚罗小妹朱银飞岳唯唯葛轲
Owner SHANXI C&Y PHARMACEUTICAL GROUP CO LTD
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