CN113834891B - Method for detecting phenylphosphine compounds in medicine - Google Patents
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Abstract
The application provides a detection method of phenylphosphine compounds in a drug, wherein a test solution is measured by adopting a liquid chromatography, wherein the chromatographic column is a phenyl chromatographic column, a mobile phase A is water, a mobile phase B is a mixed polar organic solvent, and the elution mode is isocratic elution. The application verifies the specificity, linearity and range, detection limit and quantification limit, precision, accuracy, stability and durability of the detection method, confirms that the detection method meets the evaluation requirement of methodology, can be used for determining the content of phenylphosphine compounds in the medicine, and provides a basis for medicine quality evaluation.
Description
Technical Field
The application belongs to the technical field of drug analysis, and particularly relates to a detection method of phenylphosphine compounds in drugs.
Background
Genotoxic impurities refer to compounds that themselves directly or indirectly damage cellular DNA, produce genetic mutations or in vivo mutagenesis, and have carcinogenic potential or propensity. Because of strong toxicity, the drug safety is strongly threatened, and in recent years, more and more cases occur that a large range of medical accidents occur because trace genotoxic impurity residues are found in marketed drugs, and the drug delivery factory causes huge economic loss.
The phenylphosphine compounds are often applied to the fields of medical industry, organic synthesis, analysis and the like, and have strong neurotoxicity to human bodies. Therefore, there is a need in the medical field to develop assays for phenylphosphines to better assess risk to patients. However, the prior art lacks a detection method for phenylphosphine compounds, such compounds are not easy to be detected accurately, and the quality of related medicines still has serious potential safety hazards.
Disclosure of Invention
In view of this, the application provides a method for detecting phenylphosphine compounds in drugs, which can be used for content determination of the phenylphosphine compounds in the drugs and provides a basis for drug quality assessment.
The specific technical scheme of the application is as follows:
the application provides a method for detecting phenylphosphine compounds in a drug, wherein a test solution is measured by adopting a liquid chromatography, wherein the chromatographic column is a phenyl chromatographic column, a mobile phase A is water, a mobile phase B is a mixed polar organic solvent, and the elution mode is isocratic elution.
Preferably, the mixed polar organic solvent comprises a first organic solvent and a second organic solvent, wherein the first organic solvent is selected from one of acetonitrile, methanol and ethanol, and the second organic solvent is selected from one of tetrahydrofuran and dichloromethane;
the volume ratio of the first organic solvent to the second organic solvent is (5-10): 1.
preferably, the first organic solvent is acetonitrile, the second organic solvent is tetrahydrofuran, and the volume ratio of acetonitrile to tetrahydrofuran is 9: 1.
preferably, in the isocratic elution, the volume ratio of the mobile phase A to the mobile phase B is 20: 80.
Preferably, the flow rate of the mobile phase of the liquid chromatography is 0.8-1.2 ml/min, and the sample injection amount is 10-50 mu l. More preferably, the mobile phase flow rate of the liquid chromatography is 1.0ml/min, and the sample amount is 50. mu.l.
Preferably, the detection wavelength of the liquid chromatography is 220-260 nm. More preferably, the detection wavelength of the liquid chromatography is 254 nm.
Preferably, the preparation method of the test solution comprises the following steps:
dissolving the sample with mobile phase eluent and diluting;
in the mobile phase eluent, a mobile phase A is water, a mobile phase B is tetrahydrofuran and acetonitrile, and the volume ratio of the acetonitrile to the tetrahydrofuran is (5-10): 1;
the volume ratio of the mobile phase A to the mobile phase B is (10-20) to (80-90).
Preferably, the concentration of the test sample in the test sample solution is 10-50 mg/ml.
Preferably, the preparation method of the control solution in the liquid chromatography comprises the following steps:
dissolving the sample with mobile phase eluent and diluting;
in the mobile phase eluent, a mobile phase A is water, a mobile phase B is tetrahydrofuran and acetonitrile, and the volume ratio of the acetonitrile to the tetrahydrofuran is (5-10): 1;
the volume ratio of the mobile phase A to the mobile phase B is (10-20) to (80-90);
the concentration of the reference substance in the reference substance solution is 10-200 ng/ml.
Preferably, the phenylphosphine compound has a structure shown in formula I:
In summary, the application provides a method for detecting phenylphosphine compounds in drugs, a test solution is determined by liquid chromatography, wherein the chromatographic column is a phenyl chromatographic column, the mobile phase a is water, the mobile phase B is a mixed polar organic solvent, and the elution mode is isocratic elution. The application verifies the specificity, linearity and range, detection limit and quantification limit, precision, accuracy, stability and durability of the detection method, confirms that the detection method meets the evaluation requirement of methodology, can be used for determining the content of phenylphosphine compounds in the medicine, and provides a basis for medicine quality evaluation.
Drawings
In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings needed to be used in the description of the embodiments or the prior art will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present application, and it is obvious for those skilled in the art that other drawings can be obtained according to the drawings without inventive exercise.
FIG. 1 is a chromatogram of a control solution of example 2 of the present application;
FIG. 2 is a chromatogram of a labeled test sample solution of example 2 of the present application;
FIG. 3 is a chromatogram of comparative example 1 of the present application;
FIG. 4 is a chromatogram of comparative example 2 of the present application;
FIG. 5 is a chromatogram of comparative example 3 of the present application;
FIG. 6 is a chromatogram of comparative example 4 of the present application;
FIG. 7 is a chromatogram of comparative example 5 of the present application;
FIG. 8 is a chromatogram of comparative example 6 of the present application;
FIG. 9 is a chromatogram of comparative example 7 of the present application;
FIG. 10 is a chromatogram of comparative example 8 of the present application;
FIG. 11 is a chromatogram of comparative example 9 of the present application (pure acetonitrile);
FIG. 12 is a chromatogram of comparative example 9 of the present application (50% acetonitrile);
FIG. 13 is a chromatogram of comparative example 9 of the present application (90% acetonitrile);
FIG. 14 is a chromatogram of comparative example 10 of the present application.
Detailed Description
In order to make the objects, features and advantages of the present application more obvious and understandable, the technical solutions in the embodiments of the present application are clearly and completely described, and it is obvious that the embodiments described below are only a part of the embodiments of the present application, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.
The reagents and raw materials used in the examples of the present application are commercially available or self-made.
Example 1
The embodiment of the application provides a method for detecting phenylphosphine compounds in a drug, which comprises the following steps:
1. the liquid chromatography conditions were as follows:
a chromatographic column: agilent Eclipse XDB-Phenyl (4.6X 250mm, 5 μm); detection wavelength: 254 nm; flow rate: 1.0 ml/min; mobile phase A: water; mobile phase B: tetrahydrofuran-acetonitrile (1: 9); and (3) an elution mode: isocratic elution, mobile phase a — mobile phase B (20: 80);
2. accurately weighing about 0.2g of orlistat raw material medicine, placing the orlistat raw material medicine into a 10ml volumetric flask, adding mobile phase eluent (the volume ratio of the mobile phase A to the mobile phase B is 20: 80) to dissolve and dilute the orlistat raw material medicine to scale, and shaking up to obtain a test solution;
3. accurately weighing a proper amount of (R) -1,1 '-binaphthyl-2, 2' -bis-diphenylphosphine reference substance, placing the reference substance in a 20ml volumetric flask, adding 5ml of tetrahydrofuran solution to dissolve, diluting the reference substance to a scale with acetonitrile, and shaking up to obtain a reference substance stock solution. Accurately weighing appropriate amount of reference stock solution in different volumetric flasks, diluting with mobile phase eluent to scale, and shaking to obtain reference solutions with concentrations of 0.0159, 0.0398, 0.0637, 0.0796, 0.1195 and 0.1593 μ g/ml.
4. Accurately weighing about 0.192g of orlistat raw material medicine, placing the orlistat raw material medicine into a 10ml volumetric flask, firstly adding a proper amount of mobile phase eluent to dissolve the orlistat raw material medicine, then respectively and accurately adding 0.2, 0.5, 1 and 1.5 ml of control solution with the concentration of 0.806 mu g/ml, then diluting the reference solution to a scale by using the mobile phase eluent, and shaking the reference solution uniformly to obtain the sample solution with the limit concentrations of 20%, 50%, 100% and 150%.
5. And respectively injecting the reference substance solution and the test solution into a liquid chromatograph for detection, and calculating to obtain the content of the phenylphosphine compound in the medicine.
Example 2
The embodiment of the application verifies the specificity of the method:
the mobile phase eluate, the control solution (0.0796. mu.g/ml) and the spiked test sample solution were each analyzed according to the test conditions of step 1 of example 1. The result shows that the (R) -1,1 '-binaphthyl-2, 2' -bis-diphenylphosphine is not detected in the blank solution chromatogram, and the detection is not interfered; in the chromatogram of the test solution, the (R) -1,1 '-binaphthyl-2, 2' -bis-diphenylphosphine is not detected; the chromatogram of the control solution with 100% limit concentration shows the peak of (R) -1,1 '-binaphthyl-2, 2' -bis-diphenylphosphine (see figure 1); the minimum separation degree of the (R) -1,1 '-binaphthyl-2, 2' -bisdiphenylphosphine peak from the adjacent peak with the peak area larger than LOQ in the chromatogram of the 100% limit concentration standard sample solution is 5.1 (see FIG. 2). The results all meet the requirements, and the detection method is proved to have good specificity.
Example 3
The embodiment of the application verifies the linearity and range of the method:
and (3) taking a standard curve solution with the concentration of 0.0159-0.1593 mu g/ml, and carrying out sample injection detection according to the analysis method in the step 1 of the embodiment 1. The results show that: in the range of 0.0159 mu g/ml-0.1593 mu g/ml (equivalent to 20% -200% of limit concentration), the peak area of (R) -1,1 '-binaphthyl-2, 2' -bis-diphenylphosphine and the concentration have good linear relation, and the correlation coefficient R is 0.9998; the ratio of the absolute value of the y-axis intercept to the response value of the 100% limit concentration is 0.2%, and the linearity meets the requirement.
Example 4
The embodiment of the application verifies the detection limit and the quantification limit of the method:
control solutions with a concentration of 0.0080. mu.g/ml and 0.0159. mu.g/ml were taken, and sample injection was performed 3 times and 6 times, respectively, in succession according to the test conditions of step 1 of example 1, and chromatograms were recorded. The results show that: the concentration of (R) -1,1 '-binaphthyl-2, 2' -bis-diphenylphosphine in the continuous 3-needle detection limiting solution is 0.0080 mu g/ml, which is equivalent to 10% of the limiting concentration, and the S/N is within the range of 12.8-14.5; the concentration of (R) -1,1 '-binaphthyl-2, 2' -bis-diphenylphosphine in the continuous 6-pin quantitative limiting solution is 0.0159 mu g/ml, which is about 20 percent of the limiting concentration, the S/N is within the range of 20.7-31.8, and the RSD of the peak area is 2.4 percent; the detection limit and the quantification limit result of the method meet the requirements.
Example 5
The embodiment of the application verifies the precision of the method:
the labeled test sample solution was taken, and the measurement was repeated 6 times in accordance with the analytical method of step 1 of example 1, and the chromatogram was recorded. The result shows that the recovery rate of (R) -1,1 '-binaphthyl-2, 2' -bis-diphenylphosphine in 6 parts of the standard sample solution with 100% limit concentration ranges from 95.8% to 97.0%, the RSD of the recovery rate is 0.5%, and the method has good repeatability.
Example 6
The embodiment of the application verifies the accuracy of the method:
the solution of the standard sample is taken, and is subjected to sample injection for 1 time respectively according to the test conditions of the step 1 in the example 1, and then analysis is performed, a chromatogram is recorded, and the recovery rate is calculated, and the result is shown in the following table 1.
TABLE 1
The results show that: the recovery rate range of (R) -1,1 '-binaphthyl-2, 2' -bis-diphenylphosphine in 3 parts of the sample solution with the limit concentration of 20% is 95.0-111.8%, and the RSD of the recovery rate is 8.3%; the recovery rate range of (R) -1,1 '-binaphthyl-2, 2' -bis-diphenylphosphine in the 50%, 100% and 150% limit concentration standard sample solution (9 parts of solution in total) is 95.3% -97.0%, the RSD of the recovery rate is 0.7%, and the accuracy result meets the requirement.
Example 7
The embodiment of the application verifies the stability of the method:
the sample solution, the control solution with a concentration of 0.0796 μ g/ml, and the sample solution with the added standard were placed in the dark at room temperature for different periods of time, and were subjected to sample injection analysis according to the analysis method of step 1 in example 1, and the recovery rate was recorded, and the results are shown in table 2 below.
TABLE 2
The result shows that the sample is placed for 53.5 hours at room temperature in a dark condition, and (1) no (R) -1,1 '-binaphthyl-2, 2' -bis-diphenylphosphine is detected in the sample solution; (2) the ratio of the detection concentration of (R) -1,1 '-binaphthyl-2, 2' -bis-diphenylphosphine in the reference solution with 100% of limit concentration to the initial (0 h) detection concentration is between 99.1% and 101.7%; (3) the ratio of the detection concentration of (R) -1,1 '-binaphthyl-2, 2' -bis-diphenylphosphine in the 100% limit concentration standard sample solution to the initial (0 h) detection concentration is between 99.0% and 101.7%; therefore, the test solution, the 100% limiting concentration control solution and the 100% limiting concentration standard test solution are stable for at least 53.5 hours under the condition of room temperature and light protection.
Example 8
The embodiment of the application verifies the durability of the method:
the column temperature fluctuates within the range of 32-38 ℃, the flow rate fluctuates within the range of 0.8-1.2 ml/min, the sample introduction analysis is carried out on the 100% limit concentration standard sample solution, the chromatogram is recorded, the recovery rate of the target compound in the 100% limit concentration standard sample solution is calculated, and the results are shown in the following table 3.
TABLE 3
The results show that: the column temperature fluctuates within the range of 32-38 ℃, the flow rate fluctuates within the range of 0.8-1.2 ml/min, the RSD range of the peak area of (R) -1,1 '-binaphthyl-2, 2' -bis-diphenylphosphine in the system applicability solution is 0.6-0.9%, and the RSD of the retention time is 0.1%; no target compound is detected in the test solution, and the detection result is consistent with that under the standard condition; the recovery rate of (R) -1,1 '-binaphthyl-2, 2' -bis-diphenylphosphine in the sample solution with the 100% limit concentration is 93.9-96.1%; the method has good durability.
Comparative example 1
Referring to the test method of example 1, the only difference is that the column in the liquid chromatography conditions of step 1 was replaced with an Agela Technologies Venusil XBP C18 column, both mobile phases A and B were replaced with acetonitrile, and the solvent in step 3 was diluted by dissolution with acetonitrile only and tested by loading with 50pppm of a control solution. The results are shown in fig. 3, and the peak appears at 2.533 min, 3.107 min and 3.923min, and the analyte is split into 3 peaks due to the solvent effect, so that accurate determination cannot be realized.
Comparative example 2
Referring to the test method of example 1, the only difference is that the mobile phase B in the step 1 liquid chromatography conditions was replaced with acetonitrile, the column in the step 1 liquid chromatography conditions was replaced with an Agela Technologies Venusil XBP C18 column, and the solvent in step 3 was dissolved and diluted with acetonitrile only and tested in a sample of 50pppm of control solution. The results are shown in FIG. 4, and the control was still split into 3 peaks and an accurate determination could not be achieved.
Comparative example 3
Referring to the detection method of example 1, the only difference is that the mobile phase B in the step 1 liquid chromatography conditions was replaced with acetonitrile, the chromatography column in the step 1 liquid chromatography conditions was replaced with an Agela Technologies Venusil XBP C18 column, and the tetrahydrofuran solution in the step 3 control solution was replaced with dichloromethane, and the following procedure was used: acetonitrile (1: 9) was diluted to the mark and tested by loading with 50pppm of a control solution. As a result, as shown in FIG. 5, the control product showed more peaks, and the peak width of the control product was increased to cause more interference.
Comparative example 4
Referring to the test method of example 1, the only difference was that the mobile phase a was replaced with tetrahydrofuran, the mobile phase B was replaced with acetonitrile in the step 1 liquid chromatography conditions, the column was replaced with an Agela Technologies Venusil XBP C18 column in the step 1 liquid chromatography conditions, and the solvent was dissolved and diluted with acetonitrile only in step 3 and tested by loading with 50pppm of a control solution. The results are shown in fig. 6, and the problem of the control being split into 3 peaks remains unsolved.
Comparative example 5
Referring to the detection method of example 1, the only difference is that both mobile phase a and mobile phase B in the liquid chromatography conditions of step 1 were replaced with acetonitrile, and the solvent in step 3 was dissolved and diluted with acetonitrile only and subjected to sample application detection with 50pppm of a control solution. The results are shown in FIG. 7, where the analyte did not split 3 peaks, but had a shoulder indicating that acetonitrile eluted less strongly as a mobile phase.
Comparative example 6
Referring to the detection method of example 1, the only difference is that the mobile phase a was replaced with tetrahydrofuran, the mobile phase B was replaced with acetonitrile in the liquid chromatography conditions of step 1, and the solvent was dissolved and diluted with acetonitrile only in step 3, and the detection was carried out by loading the sample with 50pppm of the control solution. The results are shown in fig. 8, replacing the mobile phase and not improving the shoulder problem.
Comparative example 7
Referring to the detection method of example 1, the only difference is that in the step 1 liquid chromatography conditions mobile phase a was replaced with tetrahydrofuran, mobile phase B was replaced with acetonitrile, and step 3 was performed with tetrahydrofuran: diluting with acetonitrile (1: 4), and adding a standard sample solution with 100% limit concentration for sample loading detection. The result is shown in FIG. 9, and a hetero peak appears near the target peak, which indicates that the main component of the sample interferes with the substance to be detected, and the method is not applicable.
Comparative example 8
Referring to the detection method of example 1, the difference is that the elution pattern of step 1 is adjusted to mobile phase A-mobile phase B (10: 90), and the sample solution is loaded with the sample solution of 100% limit concentration for detection. The results are shown in FIG. 10, where the baseline spectral peak is poor and the principal component interferes with the corresponding largest spectral peak when mobile phase A-mobile phase B (10: 90).
Comparative example 9
Referring to the test method of example 1, the only difference is that the solvent in step 3 is dissolved and diluted with only 50% acetonitrile aqueous solution, 90% acetonitrile aqueous solution and acetonitrile, respectively, and the test is carried out by loading the solution of the control substance with 50 pppm. The results are shown in FIGS. 11-13, where the peak width is broad when pure acetonitrile is used as the solvent (FIG. 11), and the accuracy of the results is poor. When 50% acetonitrile aqueous solution (FIG. 12) or 90% acetonitrile aqueous solution (FIG. 13) was used as the solvent, the peak shape was improved, but the blank solvent interfered with the target peak, and the separation degree between the solvent peak and the target peak was less than 1.5, so that this method was not suitable.
Comparative example 10
Referring to the test method of example 1, the only difference is that the column in the step 1 liquid chromatography conditions was replaced with an Agilent InfinityLab Poroshell EC-C18 column, and the test was loaded with a 100% limiting concentration spiked test sample solution. As shown in FIG. 14, the degree of separation between the target peak and the hetero peak is poor, the recovery rate is not satisfactory, and the sample has a target peak area larger than the limit value, which is not suitable for the method.
The above embodiments are only used for illustrating the technical solutions of the present application, and not for limiting the same; although the present application has been described in detail with reference to the foregoing embodiments, it should be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions in the embodiments of the present application.
Claims (6)
1. A detection method of phenylphosphine compounds in a medicament is characterized in that a test solution is measured by adopting a liquid chromatography, wherein the chromatographic column is a phenyl chromatographic column, a mobile phase A is water, a mobile phase B is a mixed polar organic solvent, the elution mode is isocratic elution, and the volume ratio of the mobile phase A to the mobile phase B is 20: 80;
the mixed polar organic solvent comprises a first organic solvent and a second organic solvent, wherein the first organic solvent is selected from acetonitrile, and the second organic solvent is selected from tetrahydrofuran;
the volume ratio of the first organic solvent to the second organic solvent is 9: 1;
the phenylphosphine compound has a structure shown in a formula I:
the drug is orlistat.
2. The detection method according to claim 1, wherein the flow rate of the mobile phase in the liquid chromatography is 0.8 to 1.2ml/min, and the amount of the sample is 10 to 50 μ l.
3. The detection method according to claim 1, wherein the detection wavelength of the liquid chromatography is 220 to 260 nm.
4. The detection method according to claim 1, wherein the sample solution is prepared by a method comprising:
dissolving the sample with mobile phase eluent and diluting;
in the mobile phase eluent, the mobile phase A is water, the mobile phase B is tetrahydrofuran and acetonitrile, and the volume ratio of the acetonitrile to the tetrahydrofuran is 9: 1;
the volume ratio of mobile phase a to mobile phase B was 20: 80.
5. The detection method according to claim 1, wherein the concentration of the sample in the sample solution is 10 to 50 mg/ml.
6. The detection method according to claim 1, wherein the preparation method of the control solution in the liquid chromatography comprises the following steps:
dissolving the reference substance with mobile phase eluent and diluting;
in the mobile phase eluent, the mobile phase A is water, the mobile phase B is tetrahydrofuran and acetonitrile, and the volume ratio of the acetonitrile to the tetrahydrofuran is 9: 1;
the volume ratio of the mobile phase A to the mobile phase B is 20: 80;
the concentration of the reference substance in the reference substance solution is 10-200 ng/ml.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101992076A (en) * | 2010-10-29 | 2011-03-30 | 华东理工大学 | Chiral binaphthyl chromatogram immobile phase, and preparation method and application thereof |
| WO2015066696A1 (en) * | 2013-11-04 | 2015-05-07 | Forum Pharmaceuticals Inc. | Fused morphlinopyrimidines and methods of use thereof |
| CN105738506A (en) * | 2016-02-03 | 2016-07-06 | 中山万汉医药科技有限公司 | Method for measuring degraded impurities in orlistat capsules |
| CN109298081A (en) * | 2017-07-24 | 2019-02-01 | 鲁南制药集团股份有限公司 | The measuring method of impurity A biological sample in a kind of Cetilistat |
-
2021
- 2021-11-26 CN CN202111416397.9A patent/CN113834891B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101992076A (en) * | 2010-10-29 | 2011-03-30 | 华东理工大学 | Chiral binaphthyl chromatogram immobile phase, and preparation method and application thereof |
| WO2015066696A1 (en) * | 2013-11-04 | 2015-05-07 | Forum Pharmaceuticals Inc. | Fused morphlinopyrimidines and methods of use thereof |
| CN105738506A (en) * | 2016-02-03 | 2016-07-06 | 中山万汉医药科技有限公司 | Method for measuring degraded impurities in orlistat capsules |
| CN109298081A (en) * | 2017-07-24 | 2019-02-01 | 鲁南制药集团股份有限公司 | The measuring method of impurity A biological sample in a kind of Cetilistat |
Non-Patent Citations (2)
| Title |
|---|
| Asymmetric Synthesis of (R)- and (S) -4-( Su bstituted 6enzyl)di hydrof uran-2(3H)-ones: An Application of the Ruthenium-binap t Complex-catalysed Asymmetric Hydrogenation of Alkylidenesuccinic Acids;Liming Shao等;《J. CHEM. SOC. PERKIN TRANS》;19901231;第1441-1445页 * |
| 高效液相色谱法测定4,4′-双（膦酸二甲酯）甲基联苯;吴素芳等;《光谱实验室》;20130731;第30卷(第4期);第1580-1583页 * |
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