CN111380976A - Analysis method of doxercalciferol injection - Google Patents
Analysis method of doxercalciferol injection Download PDFInfo
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- CN111380976A CN111380976A CN201911413239.0A CN201911413239A CN111380976A CN 111380976 A CN111380976 A CN 111380976A CN 201911413239 A CN201911413239 A CN 201911413239A CN 111380976 A CN111380976 A CN 111380976A
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
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- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
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- G01N30/02—Column chromatography
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- G01N30/28—Control of physical parameters of the fluid carrier
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Abstract
The invention discloses an analysis method of a doxercalciferol injection, which comprises the following steps: performing determination by high performance liquid chromatography, wherein the chromatographic column is a reversed-phase chromatographic column with medium-strength hydrophobicity and hydrogen bonding phase as chromatographic column packing, the mobile phase consists of a water phase and an organic phase, and gradient elution is set according to volume fraction; and performing quantitative analysis by using an external standard method. In the analysis method, the specification of a chromatographic column is 150 x 4.6mm and 3 microns, the detection wavelength is 265nm to 274nm, the temperature of the chromatographic column is 30 ℃ to 40 ℃, the temperature of a sample injection disc is 5 ℃, and the flow rate is 1.0ml/min to 1.7 ml/min. The method is simple and easy to implement, and can be well applied to the determination of the content of the doxercalciferol injection.
Description
FIELD
The invention relates to the technical field of drug analysis, in particular to an analysis method of a doxercalciferol injection.
Background
Doxercalciferol is a vitamin D2 analog that is active after being activated in vivo. The doxercalciferol is mainly used for treating secondary hyperparathyroidism, can effectively inhibit secretion of full-stage parathyroid hormone, and increases blood calcium and blood phosphorus concentrations to a smaller extent, so that compared with other calciferol, the doxercalcinemia and hyperphosphatemia are low in incidence rate, and are safer and more effective.
In order to ensure the subsequent development and production quality of the doxercalciferol, the quality of the bulk drugs and the preparation thereof needs to be controlled. Therefore, research on obtaining a detection method for measuring the content of the doxercalciferol is particularly urgent for pharmaceutical manufacturers. By consulting Chinese and foreign documents and patents, the existing detection method for the content of the doxercalciferol is single and is not beneficial to the control of enterprises on the product quality, so that an analysis method for effectively determining the content of the doxercalciferol is urgently needed.
SUMMARY
The present disclosure relates to a method of analyzing a doxercalciferol injection, comprising:
performing determination by high performance liquid chromatography, wherein the chromatographic column is a reversed-phase chromatographic column with medium-strength hydrophobicity and hydrogen bonding phase as chromatographic column packing, the mobile phase consists of a water phase and an organic phase, and gradient elution is set according to volume fraction; and
quantitative analysis was performed by external standard method.
Brief description of the drawings
Fig. 1 shows a chromatogram of a blank solution (methanol) of the present disclosure.
Figure 2 shows a high performance liquid chromatogram of doxercalciferol of example 1 of the present disclosure.
Figure 3 shows a high performance liquid chromatogram of doxercalciferol of example 2 of the present disclosure.
Figure 4 shows a high performance liquid chromatogram of doxercalciferol of example 3 of the present disclosure.
Detailed description of the invention
In the following description, certain specific details are included to provide a thorough understanding of various disclosed embodiments. One skilled in the relevant art will recognize, however, that the embodiments can be practiced without one or more of the specific details, or with other methods, components, materials, and so forth.
Unless otherwise required by the disclosure, throughout the specification and the appended claims, the words "comprise", "comprising", and "have" are to be construed in an open, inclusive sense, i.e., "including but not limited to".
Reference throughout the specification to "one embodiment," "an embodiment," "in another embodiment," or "in certain embodiments" means that a particular reference element, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" or "in another embodiment" or "in certain embodiments" in various places throughout this specification are not necessarily all referring to the same embodiment, and furthermore, particular elements, structures, or features may be combined in any suitable manner in one or more embodiments.
Definition of
In the present disclosure, the term "external standard method" refers to a method of quantifying by comparing response signals of a control substance and a component to be measured in a sample using a pure product of the component to be measured as the control substance.
In the present disclosure, the term "gradient elution" is also referred to as "gradient elution" or "program elution", that is, the concentration ratio of the mobile phase is changed to some extent continuously in the same analysis period.
Detailed Description
The present disclosure relates to a method of analyzing a doxercalciferol injection, comprising:
performing determination by high performance liquid chromatography, wherein the chromatographic column is a reversed-phase chromatographic column with medium-strength hydrophobicity and hydrogen bonding phase as chromatographic column packing, the mobile phase consists of a water phase and an organic phase, and gradient elution is set according to volume fraction; and
quantitative analysis was performed by external standard method.
In certain embodiments, the procedure for gradient elution is:
0min, wherein the volume ratio of water to the organic solvent is 72: 28;
35min, wherein the volume ratio of water to the organic solvent is 72: 28;
43min, wherein the volume ratio of water to the organic solvent is 83: 17;
45min, wherein the volume ratio of water to the organic solvent is 83: 17;
46min, wherein the volume ratio of water to the organic solvent is 72: 28;
and the volume ratio of water to the organic solvent is 72:28 for 55 min.
In certain embodiments, the procedure for gradient elution further comprises:
0min, wherein the volume ratio of water to the organic solvent is 70: 30;
15min, wherein the volume ratio of water to the organic solvent is 70: 30;
20min, wherein the volume ratio of water to the organic solvent is 86: 14;
25min, wherein the volume ratio of water to the organic solvent is 86: 14;
25.01min, wherein the volume ratio of water to the organic solvent is 70: 30;
and (3) 30min, wherein the volume ratio of the water to the organic solvent is 70: 30.
In certain embodiments, the organic solvent is selected from methanol, ethanol, acetonitrile, or mixtures thereof.
In certain embodiments, the organic solvent is selected from acetonitrile.
In certain embodiments, further comprising the preparation of a pre-liquid chromatography detection solution comprising:
a blank solution, wherein the blank solution is methanol;
the test solution consists of doxercalciferol injection and methanol; and
a control solution consisting of a doxercalciferol control and methanol.
In certain embodiments, the test solution has a concentration of 0.001mg/ml to 1 mg/ml.
In certain embodiments, the test solution has a concentration of 0.003 mg/ml.
In certain embodiments, the control solution is at a concentration of 0.001 to 1 mg/ml.
In certain embodiments, the control solution has a concentration of 0.003 mg/ml.
In certain embodiments, the detection wavelength of the chromatography column is from 265nm to 274 nm.
In certain embodiments, the flow rate of the chromatography column is 1.0ml/min to 1.7 ml/min.
In certain embodiments, the column temperature of the chromatography column is from 30 ℃ to 40 ℃.
In certain embodiments, the sample tray temperature is from 0 ℃ to 10 ℃.
In certain embodiments, the sample tray temperature is 5 ℃.
In certain embodiments, the sample size of the column is from 20. mu.L to 200. mu.L.
In certain embodiments, the sample size of the column is 100 μ L.
Example 1
A YMC-Pack ODS-AQ column, 150 x 4.6mm,3 μm or equivalent column was used, wherein:
the column temperature was 40 deg.C
The temperature of the sample injection disc is 5 DEG C
The detection wavelength is 265nm
The flow rate was 1.2ml/min
The mobile phase is a mixed solution of water and an organic solvent, and the elution mode is gradient elution, which is specifically shown in table 1.
TABLE 1 gradient elution
The experimental procedure was as follows:
weighing a proper amount of dulcitol raw material medicine, adding methanol for dissolving and diluting to prepare a solution containing 0.003mg/ml of dulcitol in every 1ml, and taking the solution as a content control solution; preparing a test solution by the same method. Precisely measuring 100 μ l of each of the reference solution and the sample solution, injecting into a liquid chromatograph, and recording the liquid chromatogram.
As shown in FIG. 1, the chromatogram of the blank solution is a horizontal straight line and no peak appears.
As shown in FIG. 2, the HPLC chromatogram of the sample solution shows that the peak retention time of moderately calciferol in the chromatogram is 42.268, the peak area is 290113, the sample weight of the sample is 4.96mg, the sample weight of the reference substance is 5.35mg, and the peak area is 322496.
And (3) calculating:
in the formula: au-area of peak for moderate calcitol in test solution;
as-peak area of moderate calciferol in control solution;
ms-weighing the control, mg;
mu-sample amount of the test sample, mg.
The doxercalciferol content was 97% calculated by the external standard method.
Example 2
A YMC-Pack ODS-AQ column, 150 x 4.6mm,3 μm or equivalent column was used, wherein:
the column temperature was 40 deg.C
The temperature of the sample injection disc is 5 DEG C
The detection wavelength is 274nm
The flow rate was 1.2ml/min
The mobile phase is a mixed solution of water and an organic solvent, and the elution mode is gradient elution, which is specifically shown in table 2.
TABLE 2 gradient elution
The experimental procedure was as follows:
weighing a proper amount of dulcitol raw material medicine, adding methanol for dissolving and diluting to prepare a solution containing 0.003mg/ml of dulcitol in every 1ml, and taking the solution as a content control solution; preparing a test solution by the same method. Precisely measuring 100 μ l of each of the reference solution and the sample solution, injecting into a liquid chromatograph, and recording the liquid chromatogram.
As shown in FIG. 3, the HPLC chromatogram of the sample solution shows that the peak retention time of moderately calciferol in the chromatogram is 42.268, the peak area is 261401, the sample weight of the sample is 4.75mg, the sample weight of the reference sample is 5.83mg, and the peak area is 327192.
The doxercalciferol content was 98% calculated by the external standard method.
Example 3
A YMC-Pack ODS-AQ column, 150 x 4.6mm,3 μm or equivalent column was used, wherein:
the column temperature was 40 deg.C
The temperature of the sample injection disc is 5 DEG C
The detection wavelength is 265nm
The flow rate was 1.4ml/min
The mobile phase is a mixed solution of water and an organic solvent, and the elution mode is gradient elution, which is specifically shown in table 3.
TABLE 3 gradient elution
The experimental procedure was as follows:
weighing a proper amount of dulcitol raw material medicine, adding methanol for dissolving and diluting to prepare a solution containing 0.003mg/ml of dulcitol in every 1ml, and taking the solution as a content control solution; preparing a test solution by the same method. Precisely measuring 100 μ l of each of the reference solution and the sample solution, injecting into a liquid chromatograph, and recording the liquid chromatogram.
As shown in FIG. 4, the HPLC chromatogram of the sample solution shows that the peak retention time of moderately calciferol in the chromatogram is 21.427, the peak area is 241590, the sample weight of the sample is 3.99mg, the sample weight of the reference substance is 5.14mg, and the peak area is 320709.
The doxercalciferol content was 97% calculated by the external standard method.
From the foregoing it will be appreciated that, although specific embodiments of the disclosure have been described herein for purposes of illustration, various modifications or improvements may be made by those skilled in the art without departing from the spirit and scope of the disclosure, and that such modifications or improvements are intended to be within the scope of the appended claims.
Claims (7)
1. A method of analyzing a doxercalciferol injection, comprising:
performing determination by high performance liquid chromatography, wherein the chromatographic column is a reversed-phase chromatographic column with medium-strength hydrophobicity and hydrogen bonding phase as chromatographic column packing, the mobile phase consists of water and an organic solvent, and gradient elution is arranged according to volume fraction; and
quantitative analysis was performed by external standard method.
2. The assay of claim 1, wherein the gradient elution is programmed as:
0min, wherein the volume ratio of water to the organic solvent is 72: 28;
35min, wherein the volume ratio of water to the organic solvent is 72: 28;
43min, wherein the volume ratio of water to the organic solvent is 83: 17;
45min, wherein the volume ratio of water to the organic solvent is 83: 17;
46min, wherein the volume ratio of water to the organic solvent is 72: 28;
and the volume ratio of water to the organic solvent is 72:28 for 55 min.
3. The assay of claim 1, wherein the gradient elution procedure further comprises:
0min, wherein the volume ratio of water to the organic solvent is 70: 30;
15min, wherein the volume ratio of water to the organic solvent is 70: 30;
20min, wherein the volume ratio of water to the organic solvent is 86: 14;
25min, wherein the volume ratio of water to the organic solvent is 86: 14;
25.01min, wherein the volume ratio of water to the organic solvent is 70: 30;
and (3) 30min, wherein the volume ratio of the water to the organic solvent is 70: 30.
4. An assay method according to any one of claims 1 to 3 wherein the organic solvent is selected from methanol, ethanol, acetonitrile or mixtures thereof, preferably the organic solvent is selected from acetonitrile.
5. The assay of claim 4, further comprising preparation of a pre-liquid chromatography detection solution comprising:
a blank solution, wherein the blank solution is methanol;
the test solution consists of doxercalciferol injection and methanol; and
a control solution consisting of a doxercalciferol control and methanol.
6. The assay of claim 4 or 5, wherein the test solution concentration is from 0.001mg/ml to 1mg/ml, preferably the test solution concentration is 0.003 mg/ml; the concentration of the control solution is 0.001-1 mg/ml, and the concentration of the control solution is preferably 0.003 mg/ml.
7. The assay of claim 6, wherein: the detection wavelength of the chromatographic column is 265nm to 274 nm; preferably the flow rate of the chromatographic column is from 1.0ml/min to 1.7 ml/min; the column temperature of the chromatographic column is 30 to 40 ℃; the temperature of the sample injection tray is 0-10 ℃, and preferably 5 ℃; the sample amount of the chromatographic column is 20-200 mu L, and preferably 100 mu L.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140113885A1 (en) * | 2011-01-07 | 2014-04-24 | Ravi Thadhani | Assays and methods of treatment relating to vitamin d insufficiency |
| CN105287426A (en) * | 2015-10-23 | 2016-02-03 | 郑州泰丰制药有限公司 | Doxercalciferol enteric-coated tablet and preparation method thereof |
| US20170102400A1 (en) * | 2005-04-06 | 2017-04-13 | Quest Diagnostics Investments Incorporated | Methods for detecting vitamin d metabolites by mass spectrometry |
| CN106770849A (en) * | 2016-11-29 | 2017-05-31 | 无锡福祈制药有限公司 | A kind of detection method for determining doxercalciferol and its impurities |
| CN107064359A (en) * | 2017-04-17 | 2017-08-18 | 南京健友生化制药股份有限公司 | The computational methods of content in doxercalciferol parenteral solution |
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2019
- 2019-12-31 CN CN201911413239.0A patent/CN111380976A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20170102400A1 (en) * | 2005-04-06 | 2017-04-13 | Quest Diagnostics Investments Incorporated | Methods for detecting vitamin d metabolites by mass spectrometry |
| US20140113885A1 (en) * | 2011-01-07 | 2014-04-24 | Ravi Thadhani | Assays and methods of treatment relating to vitamin d insufficiency |
| CN105287426A (en) * | 2015-10-23 | 2016-02-03 | 郑州泰丰制药有限公司 | Doxercalciferol enteric-coated tablet and preparation method thereof |
| CN106770849A (en) * | 2016-11-29 | 2017-05-31 | 无锡福祈制药有限公司 | A kind of detection method for determining doxercalciferol and its impurities |
| CN107064359A (en) * | 2017-04-17 | 2017-08-18 | 南京健友生化制药股份有限公司 | The computational methods of content in doxercalciferol parenteral solution |
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| Title |
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| NINUS SIMONZADEH ET AL: "Determination of Degradation Products of Doxercalciferol by Solid-Phase Extraction and Reversed-Phase HPLC", 《JOURNAL OF CHROMATOGRAPHIC SCIENCE》 * |
| 李琳 等: "高效液相色谱法测定1,25-二羟基维生素D_2纳米乳注射液的含量", 《现代生物医学进展》 * |
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