CN101464432A - Method for measuring Cidofovir related substance by high efficiency liquid chromatography - Google Patents
Method for measuring Cidofovir related substance by high efficiency liquid chromatography Download PDFInfo
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- CN101464432A CN101464432A CN 200710179827 CN200710179827A CN101464432A CN 101464432 A CN101464432 A CN 101464432A CN 200710179827 CN200710179827 CN 200710179827 CN 200710179827 A CN200710179827 A CN 200710179827A CN 101464432 A CN101464432 A CN 101464432A
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- cidofovir
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- methyl alcohol
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Abstract
The invention discloses a measuring method for cidofovir through efficient liquid chromatography, which selects octadecyl silane bonds and silica gel as a padding chromatographic column, takes a component solvent that is composed of methanol and an aqueous phase and takes methanol as an organic phase as a mobile phase, and can be used for quality control of cidofovir and drugs including cidofovir.
Description
Technical field
The present invention relates to the high-efficient liquid phase chromatogram process measuring method of the analytical approach of Cidofovir related substance, particularly a kind of Cidofovir related substance.
Background technology
Cidofovir is the miazines antiviral agent, is used for the treatment of acquired immune deficiency syndrome (AIDS).Molecular formula is C
8H
14N
3O
6P2H
2O, chemistry 1-[(S by name)-3-hydroxyl-2-(phosphonium mesitoyl methoxy) propyl group]-the cytimidine dihydrate, its chemical structural formula is as follows:
The main intermediate impurity of cidofovir has 4, and it generates in the building-up process of cidofovir, is very important for the quality control of final products.
Cidofovir is acid strong, usually for the strong compound of polarity, can adopt special chromatographic column, for example the quaternary ammonium salt plug; Also can adopt common chromatographic column commonly used, add corresponding ion-pairing agent.This law adopts common chromatographic column (C18 chromatographic column) to realize the mensuration of Cidofovir related substance fast and accurately, thereby has realized the control of cidofovir intermediate impurity, has guaranteed the quality controllable of cidofovir and preparation thereof, has realistic meaning.
Summary of the invention
The purpose of this invention is to provide a kind of method, can be used for the preparation process of cidofovir and the quality control of final products with high-efficient liquid phase chromatogram technique analysis mensuration Cidofovir related substance.
The invention provides a kind of method with the high-performance liquid chromatogram determination Cidofovir related substance, having adopted octadecylsilane key and silica gel generally commonly used is the chromatographic column of filler, and the mixed solvent that with methyl alcohol is organic phase and water is as moving phase.
The invention provides a kind of method of high-performance liquid chromatogram determination Cidofovir related substance, the organic phase in the moving phase is a methyl alcohol, and the ratio of methyl alcohol and water is: 30～10: 70～90
The invention provides a kind of method of high-performance liquid chromatogram determination Cidofovir related substance, the organic phase in the moving phase is a methyl alcohol, and the ratio of methyl alcohol and water is: 15: 85.
The invention provides a kind of method of high-performance liquid chromatogram determination Cidofovir related substance, described water is a phosphate buffer, and its pH scope is 3～6.
The invention provides a kind of method of high-performance liquid chromatogram determination Cidofovir related substance, described phosphate is selected from a kind of or its potpourri of sodium dihydrogen phosphate, potassium dihydrogen phosphate, ammonium dihydrogen phosphate (ADP).
The invention provides a kind of method of high-performance liquid chromatogram determination Cidofovir related substance, the kation of described aqueous phase is 0.5%～1% TBAH to reagent.
The invention provides a kind of method of high-performance liquid chromatogram determination Cidofovir related substance, described phosphate is sodium dihydrogen phosphate.
The invention provides a kind of method of high-performance liquid chromatogram determination Cidofovir related substance, can realize by the following method
It is an amount of to get cidofovir, dissolve with 10% methanol aqueous solution, be mixed with every 1ml and contain the sample solution of cidofovir 1mg, flow velocity is 1ml/min, detects wavelength 260nm, selects the C18 chromatographic column for use, 25 ℃ of column temperatures, extracting sample solution 10ul injects high performance liquid chromatograph, finishes the mensuration of Cidofovir related substance.
1) gets cidofovir or contain that the formulation samples of cidofovir is an amount of dissolves or dilute sample with 10% methanol aqueous solution, and be mixed with the sample solution that every 1ml contains cidofovir 1mg approximately.
2) flow rate of mobile phase being set is 0.5～1.5ml/min, and the flow velocity of moving phase is preferably 1ml/min; Detect wavelength 220～280nm, the optimum detection wavelength is 260nm; Select the C18 chromatographic column for use; 20～30 ℃ of chromatographic column column temperatures, column temperature the best are 25 ℃.
3) get 1) sample solution 10～30ul, preferred 10ul injects high performance liquid chromatograph, finishes the mensuration of Cidofovir related substance.
The present invention can effectively measure the related substance of cidofovir, the method simple and fast, and the sensitivity for analysis height, the result is accurately and reliably.Can be used for cidofovir and contain the quality control of the medicine of cidofovir.
Description of drawings
The liquid chromatogram of Fig. 1 cidofovir and intermediate impurity thereof
The high-efficient liquid phase chromatogram of Fig. 2 cidofovir raw material
The high-efficient liquid phase chromatogram of Fig. 3 Cidofovir injection (auxiliary material blank)
The high-efficient liquid phase chromatogram of Fig. 4 Cidofovir injection
Embodiment:
Following examples are used for further understanding the present invention, but are not limited to the scope of this enforcement.
Embodiment 1
Instrument and condition
Day island proper Tianjin LC-10ATVP pump, Tianjin, island SPD-10AVP ultraviolet-visible multiwavelength detector, RHEODYNE7725i injector and TL9900 chromatographic data workstation, chromatographic column: C18 250 * 4.6mm, 5 μ m, ultraviolet detection wavelength: 260nm, moving phase: phosphate buffer (0.1mol/L sodium dihydrogen phosphate, 1% TBAH, transferring pH with 10% phosphoric acid,diluted is 4.50)/methyl alcohol-(80-20)
Experimental procedure
Get each about 10mg of cidofovir sample and intermediate impurity thereof, place the 100ml measuring bottle, add the dissolving of 10% methanol aqueous solution and be diluted to scale, shake up, as need testing solution.Get blank reagent solution and need testing solution respectively, carry out high-efficient liquid phase analysis by above-mentioned condition, the record chromatogram the results are shown in Figure 1.
Retention time is that 8.250 minutes chromatographic peak is the chromatographic peak of cidofovir among Fig. 1, and remaining chromatographic peak is the chromatographic peak of cidofovir intermediate impurity.The chromatographic peak degree of separation of cidofovir and intermediate impurity thereof is good under these conditions, can satisfy the requirement of Chinese Pharmacopoeia.
Instrument and condition
Day island proper Tianjin LC-10ATVP pump, Tianjin, island SPD-10AVP ultraviolet-visible multiwavelength detector, RHEODYNE7725i injector and TL9900 chromatographic data workstation, chromatographic column: C18 250 * 4.6mm, 5 μ m, ultraviolet detection wavelength: 260nm, moving phase: phosphate buffer (0.1mol/L sodium dihydrogen phosphate, 1% TBAH, transferring pH with 10% phosphoric acid,diluted is 4.50)/methyl alcohol-(80-20)
Experimental procedure
Get the about 10mg of cidofovir, place the 10ml measuring bottle, add the dissolving of 10% methanol aqueous solution and be diluted to scale, shake up, as need testing solution.
Get need testing solution, carry out high-efficient liquid phase analysis according to above-mentioned condition, the record chromatogram the results are shown in Figure 2.
Retention time is that 7.683 minutes chromatographic peak is the chromatographic peak of cidofovir among Fig. 2, the single impurity of its related substance is less than 0.5%, total impurities is less than 1.0%, and the result shows that the related substance of cidofovir raw material reaches the bulk drug requirement, and this law can be used for the quality monitoring of cidofovir.
Embodiment 3
Instrument and condition
Day island proper Tianjin LC-10ATVP pump, Tianjin, island SPD-10AVP ultraviolet-visible multiwavelength detector, RHEODYNE7725i injector and TL9900 chromatographic data workstation, chromatographic column: C18 250 * 4.6mm, 5 μ m, ultraviolet detection wavelength: 260nm, moving phase: phosphate buffer (0.1mol/L sodium dihydrogen phosphate, 1% TBAH, transferring pH with 10% phosphoric acid,diluted is 4.50)/methyl alcohol-(80-20)
Experimental procedure
Get Cidofovir injection 1ml (the 5ml Cidofovir injection contains cidofovir 375mg), place the 100ml measuring bottle, add 10% methanol aqueous solution and be diluted to scale, shake up, as need testing solution.Get need testing solution, carry out high-efficient liquid phase analysis according to above-mentioned condition, and carry out the auxiliary material blank test, the results are shown in Figure 3, Fig. 4 with method.
Fig. 3 proves, the auxiliary material blank is interference measurement not, retention time is that 7.780 minutes chromatographic peak is the chromatographic peak of cidofovir among Fig. 4, the single impurity of its related substance is less than 0.5%, total impurities is less than 1.0%, the result shows that the related substance of cidofovir preparation reaches the requirement of preparation, and this law can be used for the quality monitoring of cidofovir preparation.
Claims (8)
1, a kind of method with the efficient liquid phase chromatographic analysis Cidofovir related substance, it is characterized in that with octadecylsilane key and silica gel be the chromatographic column of filler, the mixed solvent that with methyl alcohol is organic phase and water is as moving phase, and aqueous phase contains kation to reagent.
2, method according to claim 1 is characterized in that the organic phase in the moving phase is a methyl alcohol, and the ratio of methyl alcohol and water is: 30～10: 70～90
3, method according to claim 1 is characterized in that the organic phase in the moving phase is a methyl alcohol, and the ratio of methyl alcohol and water is: 15: 85.
4, according to each described method of claim 1～3, it is characterized in that described water is a phosphate buffer, its pH scope is 3～6.
5, method according to claim 1, the kation that it is characterized in that described aqueous phase are 0.5%～1% TBAH to reagent.
6, method according to claim 4 is characterized in that described phosphate is selected from a kind of or its potpourri of sodium dihydrogen phosphate, potassium dihydrogen phosphate, ammonium dihydrogen phosphate (ADP).
7, method according to claim 5 is characterized in that described phosphate is sodium dihydrogen phosphate.
8, according to each described method of claim 1～7, it is characterized in that: it is an amount of to get cidofovir, with the dissolving of 10% methanol aqueous solution, be mixed with the sample solution that every 1ml contains cidofovir 1mg approximately, flow velocity is 1ml/min, detect wavelength 260nm, select the C18 chromatographic column for use, 25 ℃ of column temperatures, extracting sample solution 10ul, inject high performance liquid chromatograph, finish the mensuration of Cidofovir related substance.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200710179827 CN101464432B (en) | 2007-12-19 | 2007-12-19 | Method for measuring Cidofovir related substance by high efficiency liquid chromatography |
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|---|---|---|---|
| CN 200710179827 CN101464432B (en) | 2007-12-19 | 2007-12-19 | Method for measuring Cidofovir related substance by high efficiency liquid chromatography |
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| CN101464432A true CN101464432A (en) | 2009-06-24 |
| CN101464432B CN101464432B (en) | 2013-06-05 |
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| CN 200710179827 Expired - Fee Related CN101464432B (en) | 2007-12-19 | 2007-12-19 | Method for measuring Cidofovir related substance by high efficiency liquid chromatography |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113009014A (en) * | 2021-02-24 | 2021-06-22 | 上海旭东海普药业有限公司 | High performance liquid detection method for 2-methoxy-5-fluorouracil impurity |
-
2007
- 2007-12-19 CN CN 200710179827 patent/CN101464432B/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113009014A (en) * | 2021-02-24 | 2021-06-22 | 上海旭东海普药业有限公司 | High performance liquid detection method for 2-methoxy-5-fluorouracil impurity |
| CN113009014B (en) * | 2021-02-24 | 2023-04-07 | 上海旭东海普药业有限公司 | High performance liquid detection method for 2-methoxy-5-fluorouracil impurities |
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| CN101464432B (en) | 2013-06-05 |
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