CN113237973A - Method for detecting content of impurities in eldecalcitol soft capsules - Google Patents

Method for detecting content of impurities in eldecalcitol soft capsules Download PDF

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CN113237973A
CN113237973A CN202110493220.2A CN202110493220A CN113237973A CN 113237973 A CN113237973 A CN 113237973A CN 202110493220 A CN202110493220 A CN 202110493220A CN 113237973 A CN113237973 A CN 113237973A
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impurities
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soft capsule
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沙薇
佘弋
吕中超
王俊杰
朱盼盼
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Zhengzhou Taifeng Pharmaceutical Co ltd
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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
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • 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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    • G01—MEASURING; TESTING
    • 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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Abstract

The invention belongs to the technical field of analytical chemistry, and particularly relates to a method for detecting the content of impurities in an eldecalcitol soft capsule. The detection method comprises the following steps: preparing a sample solution: adding the weighed contents of the eldecalcitol soft capsule into an activated solid phase extraction column for extraction, then sequentially carrying out leaching, elution, eluent collection, nitrogen blow-drying, and finally dissolving with acetonitrile to obtain a sample solution; detecting the sample solution by adopting a reversed-phase high performance liquid chromatography, wherein the detection conditions are as follows: the stationary phase of the chromatographic column is as follows: octadecylsilane chemically bonded silica; the mobile phase is as follows: taking acetonitrile and water as mobile phases, and carrying out gradient elution; and (5) sampling a sample solution, and calculating the content of impurities according to an area normalization method of a correction factor. The invention can realize the complete separation of the eldecalcitol and the impurities, the minimum separation degree is more than 1.5, the influence of the interference among the components on the accuracy of the detection result is effectively avoided, and meanwhile, the detection result is accurate and reliable.

Description

Method for detecting content of impurities in eldecalcitol soft capsules
Technical Field
The invention belongs to the technical field of analytical chemistry, and particularly relates to a method for detecting the content of impurities in an eldecalcitol soft capsule.
Background
The eldecalcitol soft capsule is a vitamin D3 derivative developed by china and foreign pharmaceutical companies, and mainly inhibits bone turnover and improves bone density and bone strength. The molecular formula of the eldecalcitol is C30H50O5The molecular weight is 490.72, the English name is (1R,2R,3R,5Z,7E) -2- (3-hydroxypyroxy) -9,10-secocholesta-5,7,10(19) -triene-1,3,25-triol, and the chemical structure is shown in figure 1.
Figure BDA0003053252060000011
When adding man-hour to the production of eldecalcitol, in order to guarantee the medicine qualification degree, need to examine the content of eldecalcitol soft capsule content impurity, current detection is compared through the chromatograph more, and unable accurate assay content influences the detection supervision to medicine quality.
In view of this, designing and manufacturing a method for accurately detecting the content of impurities is especially important in the production of the eldecalcitol soft capsule.
Disclosure of Invention
In order to overcome the problems in the prior art, the invention provides a method for detecting the content of impurities in an eldecalcitol soft capsule. The detection method can realize complete separation of the eldecalcitol and the impurities, accurately detect the content of the impurities, and effectively avoid interference among the components from influencing the accuracy of the detection result.
In order to achieve the purpose, the technical scheme of the invention is as follows:
a method for detecting the content of impurities in an eldecalcitol soft capsule comprises the following steps:
(1) preparing a sample solution: adding the weighed contents of the eldecalcitol soft capsule into an activated solid phase extraction column for extraction, then sequentially carrying out leaching, elution, eluent collection, nitrogen blow-drying, and finally dissolving with acetonitrile to obtain a sample solution;
(2) detecting the sample solution by adopting a reversed-phase high performance liquid chromatography, wherein the detection conditions are as follows: the stationary phase of the chromatographic column is as follows: octadecylsilane chemically bonded silica, and the mobile phase is as follows: acetonitrile (mobile phase B) and water (mobile phase A) are taken as mobile phases;
(3) and (5) sampling a sample solution, and calculating the content of impurities according to an area normalization method of a correction factor.
Preferably, the detection conditions of the reversed-phase high performance liquid chromatography in the step (2): the detection wavelength is 265nm, and the detection time is 75-95 min; the detection time is further preferably 85min, at which time the gradient elution is carried out according to the following table:
Figure BDA0003053252060000021
preferably, in the step (1), when the sample solution is prepared, the content is added to NH activated by n-hexane2Extracting in a solid phase extraction column, then leaching with n-hexane, eluting with methanol, collecting eluent, drying by blowing with nitrogen, and dissolving uniformly with acetonitrile to prepare a solution with the concentration of 50 mu g/ml, thereby obtaining a sample solution.
Preferably, the specification of the chromatographic column in the step (2) is as follows: the inner diameter was 4.6mm, the length was 250mm, and the filler particle size was 5 μm.
Preferably, in the step (2), the column temperature is 30 ℃, the flow rate is 1.2ml/min, and the sample injection amount is 20 mu l;
compared with the prior art, the invention has the beneficial effects that:
1. the detection method can realize complete separation of the alditol and the impurities, the minimum separation degree is more than 1.5, and the influence of interference among the components on the accuracy of a detection result is effectively avoided;
2. the method can accurately detect the impurity content in the eldecalcitol soft capsule, and the detection result has high accuracy and reliability;
3. the pretreatment of the sample in the detection method adopts a solid phase extraction method, so that the interference of medium chain triglyceride can be reduced, and the detection sensitivity can be improved.
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FIG. 1 is a liquid chromatogram of a solution for determining suitability of a system using the method of example 1;
FIG. 2 is a liquid chromatogram of a sample solution measured by the method of example 1.
Detailed Description
The present invention will be further described with reference to the following examples and the accompanying drawings, wherein the described examples are only a part of the examples of the present invention, and not all examples, and all other examples obtained by those skilled in the art without any inventive step based on the examples of the present invention are within the scope of the present invention.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, and it is understood that the present invention may be embodied in other specific forms than described herein and that a person of ordinary skill in the art will readily appreciate that the present invention is not limited to the specific embodiments disclosed below.
In the examples, methanol, acetonitrile, and n-hexane were used as chromatographies, water was used as purified water, a high performance liquid chromatograph was Thermo U3000, and an analytical balance was mettler-toledo MS105 DU.
The following examples employed the eldecalcitol soft capsules from the Henan Taifeng Biotech Co.
Example 1
The method for detecting the content of impurities in the eldecalcitol soft capsule comprises the following steps:
(1) preparation of sample solution: precisely weighing the contents (about 25 μ g of the same as the content) of the eldecalcitol soft capsule, adding the contents into NH activated by n-hexane2And (3) performing solid phase extraction in the (amino) solid phase extraction column, leaching with n-hexane, eluting with methanol, collecting eluent, drying by blowing with nitrogen, and dissolving uniformly with 0.5ml of acetonitrile at a concentration of 50 mu g/ml.
(2) Detecting the sample solution by adopting a reversed-phase high performance liquid chromatography, wherein the chromatographic determination conditions are as follows:
a chromatographic column: YMC ODS-AM, specification 4.6mm × 250mm, 5 μm;
mobile phase: gradient elution was performed with water as mobile phase a and acetonitrile as mobile phase B as per table 1.
TABLE 1 gradient elution Table
Figure BDA0003053252060000031
Flow rate: 1.2 ml/min;
column temperature: 30 ℃;
sample introduction amount: 20 mu l of the mixture;
operating time: and 85 min.
The liquid chromatogram of the resulting system-compatible solution under the above-mentioned chromatographic conditions is shown in FIG. 1. As can be seen from fig. 1, the main peak retention time of the aldocalcitol was 85min, the peak shape was good, and the tailing factor was 1.00.
As can be seen from the integration results in fig. 1, the adicalcitol and impurities can be completely separated, and the minimum separation degree is above 1.5.
(3) And (5) sampling a sample solution, and calculating the content of impurities according to an area normalization method of a correction factor. The Tachy impurity correction factor is 2.60, the Lumi impurity correction factor is 2.77, the Trans impurity correction factor is 1.0, and the prodigocalcitol correction factor is 2.22.
Calculating the formula:
Figure BDA0003053252060000032
Figure BDA0003053252060000041
in the formula AHetero compoundIs the area of the peak of the impurity (after correction) in the test solution;
Ageneral assemblyIs the sum of peak areas of all components (after correction) in the test solution;
Aithe sum of the peak areas (corrected) of the individual impurities in the test solution (excluding pre-alditol) was calculated.
FIG. 2 is a liquid chromatogram of a sample solution measured by the method of example 1, and it can be calculated from the integration result in FIG. 2 that the content of pregabalin is 4.6%, and the remaining impurities are not detected.
The following test employed the procedure of example 1.
The repeatability test of the invention:
6 parts of system applicability solution is prepared, 20 mu l of the system applicability solution is precisely measured, the solution is injected into a liquid chromatograph, a chromatogram is recorded, and the repeatability result is shown in a table 2.
TABLE 2 repeatability test results
Figure BDA0003053252060000042
The results show that no unknown impurities are detected in 6 test sample solutions, the contents of the pre-eldercalciferol, the Tachy impurities, the Lumi impurities, the Trans impurities and the total impurities (except the pre-eldercalciferol) are respectively 1.27%, 2.83%, 4.33%, 2.34% and 2.35%, and the contents are all less than 8.0%, and the method has good repeatability.
The precision test of the invention is as follows:
an eldecalcitol control solution (concentration 50. mu.g/ml) was prepared. Precisely measuring 20 μ l, injecting into liquid chromatograph, recording chromatogram, and obtaining precision result shown in Table 3.
TABLE 3 results of precision measurement
Figure BDA0003053252060000051
The result shows that the determination of the dicalciferol solution is carried out for 6 times, the RSD of the main peak area is 0.23 percent and less than 2.0 percent, and the precision of the method meets the requirement.
Stability testing of the invention:
precisely measuring 20 μ l of sample solution, standing at 5 deg.C for 0h, 4h, 12h, 24h, and 48h, respectively injecting into liquid chromatograph, recording chromatogram, and stability results are shown in Table 4.
Table 4 stability test results
Figure BDA0003053252060000052
It can be seen that the test solution is kept at 5 ℃ for 48h, only the pre-eldecalcitol is detected, the content of RSD is 0.91%, and both are less than 8.0%, and the test solution is stable when kept at 5 ℃ for 48 h.

Claims (5)

1. The method for detecting the content of impurities in the eldecalcitol soft capsule is characterized by comprising the following steps:
(1) preparing a sample solution: adding the weighed contents of the eldecalcitol soft capsule into an activated solid phase extraction column for extraction, then sequentially carrying out leaching, elution, eluent collection, nitrogen blow-drying, and finally dissolving with acetonitrile to obtain a sample solution;
(2) detecting the sample solution by adopting a reversed-phase high performance liquid chromatography, wherein the detection conditions are as follows: the stationary phase of the chromatographic column is as follows: octadecylsilane chemically bonded silica, and the mobile phase is as follows: taking acetonitrile and water as mobile phases, and carrying out gradient elution;
(3) and (5) sampling a sample solution, and calculating the content of impurities according to an area normalization method of a correction factor.
2. The method for detecting the content of impurities in the eldecalcitol soft capsule according to claim 1, wherein, when the sample solution is prepared in step (1), the content is added to NH activated by n-hexane2Extracting in a solid phase extraction column, then leaching with n-hexane, eluting with methanol, collecting eluent, drying by blowing with nitrogen, and dissolving uniformly with acetonitrile to prepare a solution with the concentration of 50 mu g/ml, thereby obtaining a sample solution.
3. The method for detecting the content of impurities in the eldecalcitol soft capsule according to claim 1, wherein the detection conditions of the reversed-phase high performance liquid chromatography in step (2): the detection wavelength is 265nm, and the detection time is 75-95 min.
4. The method for detecting the content of impurities in the eldecalcitol soft capsule according to claim 1, wherein the specification of the chromatographic column in step (2) is: the inner diameter was 4.6mm, the length was 250mm, and the filler particle size was 5 μm.
5. The method for detecting the content of impurities in the eldecalcitol soft capsule according to claim 1, wherein in step (2), the column temperature is 30 ℃, the flow rate is 1.2ml/min, and the sample amount is 20 μ l.
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