阅读说明：本技术 一种泊沙康唑肠溶片有关物质的分析方法 (Analysis method of related substances of posaconazole enteric-coated tablets ) 是由 周海峰 潘端锦 王金国 于 2020-05-28 设计创作，主要内容包括：本发明涉及一种泊沙康唑肠溶片有关物质的分析方法,包括以下步骤：稀释剂配制,流动相配制,对照品溶液配制,系统适应性溶液配制,空白辅料溶液配制,供试品储备液配制；有益效果是：通过以上分析方法测定,能准确测试泊沙康唑肠溶片中的杂质含量,达到质量控制的目的。(The invention relates to an analysis method of related substances of posaconazole enteric-coated tablets, which comprises the following steps: preparing a diluent, preparing a mobile phase, preparing a reference substance solution, preparing a system adaptability solution, preparing a blank auxiliary material solution and preparing a test article stock solution; the beneficial effects are that: the content of impurities in the posaconazole enteric-coated tablets can be accurately tested by the determination of the analysis method, so that the aim of quality control is fulfilled.)

1. An analysis method of related substances of posaconazole enteric-coated tablets is characterized by comprising the following steps: the method comprises the following steps:

preparing a diluent: taking methanol and water in a volume ratio of 4: 1, mixing;

preparing a mobile phase:

mixing the mobile phase A with trifluoroacetic acid and water,

mobile phase B, mixing acetonitrile, water and trifluoroacetic acid;

preparing a reference solution:

preparing reference substance stock solution-1, adding posaconazole into a volumetric flask, adding methanol, performing ultrasonic treatment, shaking,

preparing reference stock solution-2, adding reference stock solution-1 into volumetric flask, diluting with diluent,

preparing a reference solution, and taking a reference stock solution-2 for dilution;

preparing a sensitivity solution, and adding a diluent to dilute a reference solution to ensure that the concentration of posaconazole is 0.2 mug/mL;

preparing a system adaptive solution:

preparing a system adaptive stock solution, heating the posaconazole enteric-coated tablet, grinding, adding water for dissolving, adding methanol, oscillating, diluting,

preparing a system adaptive solution, taking a system adaptive stock solution, adding a diluent for mixing, filtering by using a filter membrane of 0.45 mu m, and collecting filtrate;

preparing a blank auxiliary material solution:

preparing blank adjuvant stock solution, adding water into blank adjuvant, adding methanol, shaking, diluting with methanol,

preparing a blank auxiliary material solution, diluting a blank auxiliary material stock solution with a diluent, filtering with a filter membrane of 0.45 mu m, and collecting filtrate;

preparing a stock solution of a test sample, namely taking the posaconazole enteric-coated tablet, adding water, oscillating, adding methanol, oscillating and diluting with methanol;

preparing a test solution, namely adding a diluent into a test stock solution, uniformly mixing, filtering by using a filter membrane of 0.45 mu m, and collecting filtrate;

measuring the peak area of the reference solution n times by a liquid chromatograph, and calculating the average value A_S，

Measuring impurity peak area A of sample solution by liquid chromatograph_T，

According to the formula

2. The method for analyzing related substances of the posaconazole enteric-coated tablet, according to claim 1, is characterized in that: acetonitrile, water, trifluoroacetic acid according to 90:10: mixing at a ratio of 0.1.

3. The method for analyzing related substances of the posaconazole enteric-coated tablet, according to claim 1, is characterized in that: preparing a system adaptive stock solution, and heating the posaconazole enteric-coated tablets at 105 ℃ for 8 +/-2 h.

4. The method for analyzing related substances of the posaconazole enteric-coated tablet, according to claim 1, is characterized in that:

the specific steps for preparing the reference solution are as follows:

preparing reference substance stock solution-1, putting posaconazole into a volumetric flask, adding methanol, performing ultrasonic treatment, shaking, diluting to scale to make the concentration of posaconazole be 100 μ g/mL,

preparing reference substance stock solution-2, adding reference substance stock solution-1 into a volumetric flask, adding a diluent to dilute to a scale so that the concentration of posaconazole is 8 mug/mL,

preparing a reference solution, taking the reference stock solution-2, and diluting to ensure that the concentration of the posaconazole is 0.8 mu g/mL.

5. The method for analyzing related substances of the posaconazole enteric-coated tablet, according to claim 1, is characterized in that: the preparation method of the test solution comprises the following specific steps:

mixing the stock solution with diluent, filtering with 0.45 μm filter membrane, discarding 2ml of the primary filtrate, and collecting the secondary filtrate.

6. The method for analyzing related substances of the posaconazole enteric-coated tablet, according to claim 1, is characterized in that:

the parameters of the liquid chromatograph are that the wavelength is 254nm, the flow rate is 1.0mL/min, and the sample injection volume is 10 mu L.

7. The method for analyzing related substances of the posaconazole enteric-coated tablet, according to claim 1, is characterized in that:

the RRF of the degraded impurity and the unknown impurity is 1.0, the RRF of the impurity PSK-1 is 0.89, and the RRF of the impurity PSK-2 is 1.24.

8. The method for analyzing related substances of the posaconazole enteric-coated tablet, according to claim 1, is characterized in that:

the preparation method of the stock solution of the test sample comprises the following specific steps: adding water into the posaconazole enteric-coated tablets, mechanically shaking for 30min at 200rpm by using an oscillator, adding methanol, ultrasonically shaking, and adding methanol for dilution.

9. The method for analyzing related substances of the posaconazole enteric-coated tablet, according to claim 1, is characterized in that:

the sample introduction sequence when using the liquid chromatograph is diluent, sensitivity solution, system applicability solution, reference solution and test solution.

Technical Field

The invention belongs to the technical field of chemical measurement and analysis, and particularly relates to an analysis method of related substances of posaconazole enteric-coated tablets.

Background

The posaconazole is a derivative of itraconazole, is a second-generation triazole antifungal drug, and is developed by American Moshadong pharmacy as an original product. The posaconazole enteric-coated tablets are listed in the first recommendation list of the encouragement imitation pharmaceutical catalogues published by the country. At present, no inspection and analysis method for the product exists in Chinese pharmacopoeia.

Disclosure of Invention

In order to solve the problems, the invention adopts the following technical scheme:

an analysis method of related substances of posaconazole enteric-coated tablets comprises the following steps:

preparing a diluent;

preparing a mobile phase, namely preparing a mobile phase,

mixing the mobile phase A with trifluoroacetic acid and water,

mobile phase B, mixing acetonitrile, water and trifluoroacetic acid;

preparing a reference solution:

preparing reference stock solution-1, putting posaconazole into a container, adding methanol, performing ultrasonic treatment, shaking,

preparing reference stock solution-2, adding reference stock solution-1 into volumetric flask, diluting with diluent,

preparing a reference solution, and taking a reference stock solution-2 for dilution;

preparing a sensitivity solution, and adding a diluent to dilute a reference solution to ensure that the concentration of posaconazole is 0.2 mug/mL;

preparing a system adaptive solution:

preparing a system adaptive stock solution, heating the posaconazole enteric-coated tablet, grinding, adding water for dissolving, adding methanol, oscillating, diluting,

preparing a system adaptive solution, taking a system adaptive stock solution, adding a diluent for mixing, filtering by using a filter membrane of 0.45 mu m, and collecting filtrate;

preparing a blank auxiliary material solution:

preparing blank adjuvant stock solution, adding water into blank adjuvant, adding methanol, shaking, diluting with methanol,

preparing a blank auxiliary material solution, diluting a blank auxiliary material stock solution with a diluent, filtering with a filter membrane of 0.45 mu m, and collecting filtrate;

preparing a stock solution of a test sample, namely taking the posaconazole enteric-coated tablet, adding water, oscillating, adding methanol, oscillating and diluting with methanol;

preparing a test solution, namely adding a diluent into a test stock solution, uniformly mixing, filtering by using a filter membrane of 0.45 mu m, and collecting filtrate;

measuring the peak area of the reference solution n times by a liquid chromatograph,calculate the average A_S，

Measuring impurity peak area A of sample solution by liquid chromatograph_T，

According to the formulaCs is the concentration of the control solution, C_tCalculating the percentage content of impurities in the posaconazole tablets by taking the RRF as a relative response factor as the concentration of the test solution.

In one mode, acetonitrile, water and trifluoroacetic acid are mixed according to a ratio of 90:10: mixing at a ratio of 0.1.

In one mode, a systematic adaptive stock solution is prepared by heating posaconazole enteric-coated tablets at 105 ℃ for 8 +/-2 h.

In one embodiment, the method for preparing the reference solution comprises the following steps:

preparing reference stock solution-1, adding posaconazole into a volumetric flask, adding methanol, performing ultrasonic treatment, shaking to make posaconazole concentration be 100 μ g/mL,

preparing reference stock solution-2, adding reference stock solution-1 into a volumetric flask, adding diluent to dilute to make the concentration of posaconazole be 8 mug/mL,

preparing a reference solution, taking the reference stock solution-2, and diluting to ensure that the concentration of the posaconazole is 0.8 mu g/mL.

In one mode, the concrete steps of preparing the test solution are as follows:

mixing the stock solution with diluent, filtering with 0.45 μm filter membrane, discarding 2ml of the primary filtrate, and collecting the secondary filtrate.

In one mode, the parameters of the liquid chromatograph are 254nm wavelength, 1.0mL/min flow rate and 10 muL sample volume.

One way, the RRF of the degraded and unknown impurities is 1.0, the RRF of the impurity PSK-1 is 0.89, and the RRF of the impurity PSK-2 is 1.24.

One way, the preparation of the stock solution of the test article comprises the following specific steps: adding water into the posaconazole enteric-coated tablets, mechanically shaking for 30min at 200rpm by using an oscillator, adding methanol, ultrasonically shaking, and adding methanol for dilution.

In one mode, the sample introduction sequence when using the liquid chromatograph is diluent, sensitivity solution, system applicability solution, reference solution, and test solution.

[ advantageous effects ]

The invention has the beneficial effects that:

the content of impurities in the posaconazole enteric-coated tablets can be accurately tested by the determination of the analysis method, so that the aim of quality control is fulfilled.

Detailed Description