CN106546668A - A kind of HPLC methods for separating good fortune department's fluconazole or its pharmaceutical salts about material - Google Patents
A kind of HPLC methods for separating good fortune department's fluconazole or its pharmaceutical salts about material Download PDFInfo
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- CN106546668A CN106546668A CN201510605057.9A CN201510605057A CN106546668A CN 106546668 A CN106546668 A CN 106546668A CN 201510605057 A CN201510605057 A CN 201510605057A CN 106546668 A CN106546668 A CN 106546668A
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- fluconazole
- good fortune
- pharmaceutical salts
- hplc methods
- fortune department
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Abstract
This method is related to a kind of HPLC methods for separating analysis good fortune department's fluconazole or its pharmaceutical salts about material, and using high performance liquid chromatography, the method can fast and effectively separate the relevant material of analysis good fortune department's fluconazole or its pharmaceutical salts.
Description
Technical field
The present invention relates to a kind of high efficient liquid phase analysis method, specifically a kind of good fortune department fluconazole or the relevant material of its pharmaceutical salts separate analysis and determine.
Background technology
Good fortune department fluconazole or its pharmaceutical salts are the prodrug of fluconazole, and good fortune department fluconazole or its pharmaceutical salts are entered and can be metabolized as fluconazole by the effect of alkali phosphatase in vivo, so as to play drug action.Fluconazole is a kind of triazole antifungal agent of wide spectrum
Its indication is as follows：Fungemia, fungus in respiratory tract disease, Fangal peritonitis, digestive tract mycosises, urinary tract mycosises, funguses meningitis.
We have found that the compound does not find separation method of the compound about material in the document published yet during exploitation good fortune department's fluconazole or its pharmaceutical salts.This present situation causes the ununified standard determined about material of the compound, greatly hinders reference and the popularization of the compound.Therefore, it is very necessary to set up a set of effective, stable relevant material separation method.
The structural formula of wherein good fortune department fluconazole or its pharmaceutical salts is as follows：
X represents Na, K, Mg, Ca, aminoacid.
The content of the invention
The purpose of the present invention is aiming at the defect of prior art, there is provided the method for separating and analyzing of a kind of good fortune department fluconazole or its pharmaceutical salts about material, and it can be precisely separating the relevant material for determining good fortune department's fluconazole or its pharmaceutical salts.
As needed, we during exploitation good fortune department's fluconazole or its pharmaceutical salts, the primary study high performance liquid chromatography separation method of good fortune department fluconazole or its pharmaceutical salts.
The method of good fortune department's fluconazole or its pharmaceutical salts about material is separated with high-efficient liquid phase chromatogram technique analysis described in this method, be the water phase with bonded silica gel as filler（PH value 1～9.5）Mobile phase is combined as with certain proportioning with organic solvent, and flow velocity is 0.1～1.5ml/min, and column temperature is 0～50 DEG C, and sampling volume is 0.1～100 μ l, eluting separation is carried out using gradient or isocratic method.The method can fast and effectively separate the relevant material of analysis good fortune department's fluconazole or its pharmaceutical salts.
Filler of the present invention is selected from following bonded silica gel：Octadecyl silane, phenyl bonded silica, cyano group bonded silica gel, amino bonded silica gel.
Organic solvent of the present invention is selected from following solvent：One or more of acetonitrile, methanol, ethanol, tetrahydrofuran, normal propyl alcohol, isopropanol.
Isocratic condition organic solvent of the present invention：The ratio of water phase is 5%～95%：95%～5%.
When gradient condition of the present invention is 0～15 minute, ratio after two-phase mixtures shared by organic faciess is 10%～40%, in 15～30 minutes sections, gradually increases organic Phase Proportion to 30%～80%, kept for 1～40 minute, then organic Phase Proportion was down to into 10%～40% in 5 minutes.
The pH value of water phase of the present invention is 1.0～9.5, and the pH value of described water phase is preferably 2.0～5.0；Most preferably 2.5～3.0.
The reagent that water of the present invention is mutually adopted include for potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium heptanesulfonate, 4-butyl ammonium hydrogen sulfate, phosphoric acid, triethylamine, TBAH, tetrabutyl ammonium bromide, sodium dihydrogen phosphate disodium hydrogen phosphate, acetic acid, one or more of trifluoroacetic acid composition water phase；Most preferably 4-butyl ammonium hydrogen sulfate and triethylamine mixed system.
Specific embodiment：
The invention will be further described with reference to embodiments, but these embodiments must not be used for explaining the restriction of the scope of the present invention.
Embodiment 1
Experimental apparatus and condition
High performance liquid chromatograph（Wear peace U3000）；Chromatographic column：Thermo Fisher BDS HYPERSIL
C18 (5μm ,4.6mm×250mm) ；Mobile phase A is acetonitrile；Mobile phase B is ion-pairing agent solution（0.008mol/L 4-butyl ammonium hydrogen sulfates, triethylamine adjust pH2.5）, gradient condition carries out linear elution, flow velocity 1.0ml/min according to following table；Detection wavelength：260nm；20 DEG C of column temperature；Take impurity biased sample sample introduction, 20 μ l of sampling volume.
As a result see the table below,
As a result each impurity can be efficiently separated with good fortune department fluconazole.
Embodiment 2
Experimental apparatus and condition
High performance liquid chromatograph（Wear peace U3000）；Chromatographic column：Phenyl post (5 μm, 4.6mm × 250mm)；Mobile phase A is acetonitrile；Mobile phase B is ion-pairing agent solution（0.010mol/L TBAH, phosphoric acid adjust pH3.0）, gradient condition carries out linear elution, flow velocity 1.0ml/min according to following table；Detection wavelength：260nm；20 DEG C of column temperature；Take impurity biased sample sample introduction, 20 μ l of sampling volume.
As a result see the table below,
As a result each impurity can be efficiently separated with good fortune department fluconazole.
Embodiment 3
Experimental apparatus and condition
High performance liquid chromatograph（Wear peace U3000）；Chromatographic column：5 μm of 150 × 4.6mm of cyano column；Mobile phase：Methanol：Phosphate buffer（0.02M potassium dihydrogen phosphates, phosphoric acid adjust pH2.0）=40:60；Flow velocity 1.0ml/min；Detection wavelength：260nm；30 DEG C of column temperature；Take impurity biased sample sample introduction, 10 μ l of sampling volume.As a result see the table below,
As a result each impurity can be efficiently separated with good fortune department fluconazole.
Embodiment 4
Experimental apparatus and condition
High performance liquid chromatograph（Wear peace U3000）；Chromatographic column：Thermo Fisher BDS HYPERSIL
C18 (5μm ,4.6mm×250mm) ；Mobile phase A is acetonitrile；Mobile phase B is ion-pairing agent solution（0.005mol/L 4-butyl ammonium hydrogen sulfates, triethylamine adjust pH2.5）, gradient condition carries out linear elution, flow velocity 1.0ml/min according to following table；Detection wavelength：260nm；25 DEG C of column temperature；Take impurity biased sample sample introduction, 20 μ l of sampling volume.
As a result see the table below,
As a result each impurity can be efficiently separated with good fortune department fluconazole.
Claims (7)
1. a kind of HPLC methods for separating good fortune department's fluconazole or its pharmaceutical salts about material, it is characterized in that with bonded silica gel as filler, water phase is combined as mobile phase with certain proportioning with organic solvent, flow velocity is 0.1～1.5ml/min, column temperature is 0～50 DEG C, sampling volume is 0.1～100 μ l, carries out eluting separation using gradient or isocratic method.
2. HPLC methods for separating good fortune department fluconazole or its pharmaceutical salts about material according to claim 1, it is characterised in that described bonded silica gel is octadecyl silane, phenyl bonded silica, cyano group bonded silica gel, amino bonded silica gel.
3. HPLC methods for separating good fortune department fluconazole or its pharmaceutical salts about material according to claim 1, it is characterised in that the reagent that described water is mutually adopted include for potassium dihydrogen phosphate, dipotassium hydrogen phosphate, sodium heptanesulfonate, 4-butyl ammonium hydrogen sulfate, phosphoric acid, triethylamine, TBAH, tetrabutyl ammonium bromide, sodium dihydrogen phosphate disodium hydrogen phosphate, acetic acid, trifluoroacetic acid the water phase for constituting for one or more.
4. HPLC methods for separating good fortune department fluconazole or its pharmaceutical salts about material according to claim 1, it is characterised in that the pH value of described water phase is 1～9.5, preferably 2.0～5.0；Most preferably 2.5～3.0.
5. HPLC methods for separating good fortune department fluconazole or its pharmaceutical salts about material according to claim 1, it is characterised in that the organic solvent is one or more of acetonitrile, methanol, ethanol, tetrahydrofuran, normal propyl alcohol, isopropanol.
6. HPLC methods for separating good fortune department fluconazole or its pharmaceutical salts about material according to claim 1, it is characterised in that described isocratic method is organic solvent：The ratio of water phase is 5%～95%：95%～5%.
7. HPLC methods for separating good fortune department's fluconazole or its pharmaceutical salts about material according to claim 1, it is characterized in that when described gradient method is 0～15 minute, ratio after two-phase mixtures shared by organic faciess is 10%～40%, in 15～30 minutes sections, gradually increase organic Phase Proportion to 30%～80%, kept for 1～40 minute, then organic Phase Proportion was down to into 10%～40% in 5 minutes.
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| CN201510605057.9A CN106546668A (en) | 2015-09-22 | 2015-09-22 | A kind of HPLC methods for separating good fortune department's fluconazole or its pharmaceutical salts about material |
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| CN201510605057.9A CN106546668A (en) | 2015-09-22 | 2015-09-22 | A kind of HPLC methods for separating good fortune department's fluconazole or its pharmaceutical salts about material |
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1210540A (en) * | 1996-02-02 | 1999-03-10 | 辉瑞研究开发公司 | Triazole derivatives useful in therapy |
| CN101389333A (en) * | 2006-02-22 | 2009-03-18 | 卫材R&D管理有限公司 | Stabilized pharmaceutical composition |
| MX2011008204A (en) * | 2009-02-05 | 2011-12-06 | Targeted Delivery Technologies Ltd | Methods of reducing the proliferation and viability of microbial agents. |
| CN102439018A (en) * | 2009-03-19 | 2012-05-02 | 塞普斯制药有限公司 | Fosfluconazole derivatives, synthesis, and use in long acting formulations |
| CN103864844A (en) * | 2012-12-09 | 2014-06-18 | 正大天晴药业集团股份有限公司 | Preparation method of fosfluconazole |
| CN104650140A (en) * | 2013-11-18 | 2015-05-27 | 正大天晴药业集团股份有限公司 | Preparation method of high purity fosfluconazole |
| CN104860992A (en) * | 2014-02-25 | 2015-08-26 | 陕西合成药业股份有限公司 | Preparation method of high-purity fosfluconazole |
| CN104873468A (en) * | 2014-02-27 | 2015-09-02 | 陕西合成药业股份有限公司 | Fosfluconazole for injection, a preparing method thereof and uses of the fosfluconazole |
-
2015
- 2015-09-22 CN CN201510605057.9A patent/CN106546668A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1210540A (en) * | 1996-02-02 | 1999-03-10 | 辉瑞研究开发公司 | Triazole derivatives useful in therapy |
| CN101389333A (en) * | 2006-02-22 | 2009-03-18 | 卫材R&D管理有限公司 | Stabilized pharmaceutical composition |
| MX2011008204A (en) * | 2009-02-05 | 2011-12-06 | Targeted Delivery Technologies Ltd | Methods of reducing the proliferation and viability of microbial agents. |
| CN102439018A (en) * | 2009-03-19 | 2012-05-02 | 塞普斯制药有限公司 | Fosfluconazole derivatives, synthesis, and use in long acting formulations |
| CN103864844A (en) * | 2012-12-09 | 2014-06-18 | 正大天晴药业集团股份有限公司 | Preparation method of fosfluconazole |
| CN104650140A (en) * | 2013-11-18 | 2015-05-27 | 正大天晴药业集团股份有限公司 | Preparation method of high purity fosfluconazole |
| CN104860992A (en) * | 2014-02-25 | 2015-08-26 | 陕西合成药业股份有限公司 | Preparation method of high-purity fosfluconazole |
| CN104873468A (en) * | 2014-02-27 | 2015-09-02 | 陕西合成药业股份有限公司 | Fosfluconazole for injection, a preparing method thereof and uses of the fosfluconazole |
Non-Patent Citations (3)
| Title |
|---|
| TAKAHIKO AOYAMA 等: "Pharmacokinetics of Fluconazole and Fosfluconazole after Intraperitoneal Administration to Peritoneal Dialysis Rats", 《DRUG METAB. PHARMACOKINET》 * |
| 国大亮 等: "福司氟康唑", 《齐鲁药事》 * |
| 王琰 等: "磷氟康唑有关物质分析方法的筛选与优化", 《药物分析杂志》 * |
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