CN118777441A - Method for detecting content of fenofibric acid choline slow-release capsules - Google Patents
Method for detecting content of fenofibric acid choline slow-release capsules Download PDFInfo
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- CN118777441A CN118777441A CN202310366542.XA CN202310366542A CN118777441A CN 118777441 A CN118777441 A CN 118777441A CN 202310366542 A CN202310366542 A CN 202310366542A CN 118777441 A CN118777441 A CN 118777441A
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- 229960000701 fenofibric acid Drugs 0.000 title claims abstract description 62
- MQOBSOSZFYZQOK-UHFFFAOYSA-N fenofibric acid Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C(=O)C1=CC=C(Cl)C=C1 MQOBSOSZFYZQOK-UHFFFAOYSA-N 0.000 title claims abstract description 62
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 title claims abstract description 58
- 229960001231 choline Drugs 0.000 title claims abstract description 58
- 239000002775 capsule Substances 0.000 title claims abstract description 33
- 238000000034 method Methods 0.000 title claims abstract description 28
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract description 58
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 41
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims abstract description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 238000001514 detection method Methods 0.000 claims abstract description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 6
- 239000000945 filler Substances 0.000 claims abstract description 3
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 3
- 239000002904 solvent Substances 0.000 claims description 56
- 239000000243 solution Substances 0.000 claims description 55
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 36
- 238000005303 weighing Methods 0.000 claims description 25
- 238000007865 diluting Methods 0.000 claims description 20
- 239000012488 sample solution Substances 0.000 claims description 17
- 239000013558 reference substance Substances 0.000 claims description 15
- 238000009210 therapy by ultrasound Methods 0.000 claims description 14
- 239000007788 liquid Substances 0.000 claims description 12
- 239000006228 supernatant Substances 0.000 claims description 12
- 238000010829 isocratic elution Methods 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 7
- 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 claims description 4
- 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 claims description 4
- 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 claims description 4
- 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 claims description 4
- 238000005286 illumination Methods 0.000 claims description 4
- 239000012085 test solution Substances 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 3
- 238000010790 dilution Methods 0.000 claims description 3
- 239000012895 dilution Substances 0.000 claims description 3
- MZTKIKBXDMDCDY-UHFFFAOYSA-N 2-[4-(4-hydroxybenzoyl)phenoxy]-2-methylpropanoic acid Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1C(=O)C1=CC=C(O)C=C1 MZTKIKBXDMDCDY-UHFFFAOYSA-N 0.000 claims 1
- 238000013265 extended release Methods 0.000 claims 1
- 238000004458 analytical method Methods 0.000 abstract description 6
- 238000000605 extraction Methods 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 4
- 239000003085 diluting agent Substances 0.000 abstract 1
- 238000005259 measurement Methods 0.000 abstract 1
- 239000012071 phase Substances 0.000 description 41
- 239000002994 raw material Substances 0.000 description 20
- 239000012535 impurity Substances 0.000 description 13
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 10
- 229960002297 fenofibrate Drugs 0.000 description 9
- 238000011835 investigation Methods 0.000 description 7
- 238000001782 photodegradation Methods 0.000 description 7
- 238000011084 recovery Methods 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 239000000463 material Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 238000000926 separation method Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 238000010586 diagram Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000012088 reference solution Substances 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- ILPUOPPYSQEBNJ-UHFFFAOYSA-N 2-methyl-2-phenoxypropanoic acid Chemical class OC(=O)C(C)(C)OC1=CC=CC=C1 ILPUOPPYSQEBNJ-UHFFFAOYSA-N 0.000 description 1
- 239000004381 Choline salt Substances 0.000 description 1
- 102000023984 PPAR alpha Human genes 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 230000001315 anti-hyperlipaemic effect Effects 0.000 description 1
- 235000019417 choline salt Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 238000000527 sonication Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000002137 ultrasound extraction Methods 0.000 description 1
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- Treatment Of Liquids With Adsorbents In General (AREA)
Abstract
The invention belongs to the field of medicine detection, and relates to a method for detecting the content of a fenofibric acid choline slow-release capsule, which comprises the following steps: quantitatively detecting the fenofibric acid choline slow-release capsule by adopting high performance liquid chromatography; the conditions of high performance liquid chromatography include: chromatographic column: a chromatographic column using octadecylsilane chemically bonded silica as a filler; mobile phase: water (phosphoric acid to adjust pH to 2.5) -acetonitrile (45:55); flow rate: 1.0ml/min; column temperature: 35 ℃; detection wavelength: 286nm; a diluent: water (phosphoric acid to adjust pH to 2.5) -acetonitrile (1:1). The detection method provided by the invention shortens the analysis time and improves the analysis efficiency while meeting the specificity, and develops an extraction mode for the content measurement of the fenofibric acid choline slow-release capsule.
Description
Technical Field
The invention belongs to the field of medicine detection, and relates to a method for detecting the content of a fenofibric acid choline slow-release capsule.
Background
Fenofibrate choline is a choline salt of fenofibric acid. Fenofibrate is a synthetic phenoxyisobutyric acid derivative, has antihyperlipidemic activity, and is a PPARα agonist.
Proved by a large number of clinical experiments and drug researches: the hydrophobicity of the fenofibrate leads to low bioavailability, is greatly influenced by food, and in contrast to the fenofibrate, the fenofibrate choline has higher solubility in small intestine areas, so that the bioavailability of the fenofibric acid is increased, the bioavailability is not influenced by food, and simultaneously, the dosage is reduced, and the toxic and side effects are also reduced. The chemically modified fenofibrate choline is an ultimate solution for the bioavailability of the fenofibrate, and can be expected to replace all the prior fenofibrate preparations on the market, greatly improve the curative effect and reduce the toxicity.
The control of the product content is critical to the quality control of the product, and the method for detecting the content of the fenofibrate choline slow-release capsule does not have any pharmacopoeia standard at present, and the method adopted at present has the problems that the chromatographic condition analysis time is long, the preparation mode of the test sample is not applicable to the fenofibrate choline slow-release capsule, and the like. In order to ensure the quality of the preparation in the research, production, storage, sale and use processes and ensure the safety and effectiveness of medicines, a method capable of meeting the content detection of the fenofibric acid choline slow-release capsule is needed to be provided.
Disclosure of Invention
In order to solve the technical problems, the invention provides a method for detecting the content of the fenofibric acid choline slow-release capsule, which shortens the analysis time, improves the analysis efficiency compared with the prior art, and simultaneously develops a method for extracting and preparing a sample suitable for the fenofibric acid choline slow-release capsule.
The method for detecting the content of the fenofibric acid choline slow-release capsule comprises the following steps of:
quantitatively detecting the content of the fenofibric acid choline slow-release capsule by adopting high performance liquid chromatography;
the conditions of high performance liquid chromatography include:
chromatographic column: a chromatographic column using octadecylsilane chemically bonded silica as a filler;
Mobile phase a: water;
Mobile phase B: acetonitrile;
flow rate: 1.0ml/min;
column temperature: 35 ℃;
detection wavelength: 286nm;
blank solvent: mobile phase a-mobile phase B;
The system applicability solution is placed for 30 to 50 minutes under 5000 to 7000lx illumination after being prepared; the sample solution is subjected to ultrasonic treatment before dilution.
Further, an isocratic elution mode is adopted, and the isocratic elution proportion mobile phase A: mobile phase B was 45:55.
Further, the system applicability solution was left under 5000lx light for 30min after being formulated.
Further, the preparation method of the system applicability solution comprises the following steps: precisely weighing 13mg of fenofibric acid choline reference substance, placing into a 100ml transparent measuring flask, adding solvent to dilute to scale, shaking, standing under 5000lx illumination for 30min, and taking out to obtain a system applicability solution.
Further, the sonication time is at least 20 minutes.
Further, the linear equation is y= 15365512.1359x-8458.2762, and the correlation coefficient r is 0.9999.
Further, the chromatographic column adopts: SYMMETRYSHIELD TM RP18, 4.6X250 mm,5 μm.
Further, the sample solution and the reference solution are respectively injected into a liquid chromatograph, and a chromatogram is recorded, and the preparation method of the sample solution and the reference solution is as follows:
taking a proper amount of the content of the product (about 135mg equivalent to fenofibric acid), precisely weighing, placing into a 100ml measuring flask, adding 20ml of methanol, performing ultrasonic treatment for 20 minutes to completely disintegrate, cooling to room temperature, diluting to a scale with a solvent, shaking uniformly, centrifuging, precisely weighing 1ml of supernatant, placing into a 10ml measuring flask, diluting to the scale with the solvent, shaking uniformly, and taking the supernatant as a sample solution.
Taking a proper amount of a fenofibric acid choline reference substance, precisely weighing, dissolving with a solvent, and diluting to prepare a solution containing 0.13mg of fenofibric acid per 1ml, wherein the solution is used as a reference substance solution.
Further, the volume ratio of mobile phase A to mobile phase B in the blank solvent is 1:1.
Further, in mobile phase a, phosphoric acid was used to adjust the pH of water to 2.5.
The method for detecting the content of the fenofibric acid choline slow-release capsule comprises the following steps of:
(1) Preparing a solution:
1L of mobile phase A and 1L of mobile phase B are measured and uniformly mixed to be used as blank solvent;
Precisely weighing 13mg of fenofibric acid choline reference substance, placing into a 100ml transparent measuring flask, adding solvent to dilute to scale, and shaking. Placing under 5000lx light for 30min, taking out, and taking out to obtain system applicability solution.
Taking a proper amount of the content of the product (about 135mg equivalent to fenofibric acid), precisely weighing, placing into a 100ml measuring flask, adding 20ml of methanol, performing ultrasonic treatment for 20 minutes to completely disintegrate, cooling to room temperature, diluting to a scale with a solvent, shaking uniformly, centrifuging, precisely weighing 1ml of supernatant, placing into a 10ml measuring flask, diluting to the scale with the solvent, shaking uniformly, and taking the supernatant as a sample solution.
Taking a proper amount of a fenofibric acid choline reference substance, precisely weighing, dissolving with a solvent, and diluting to prepare a solution containing 0.13mg of fenofibric acid per 1ml, wherein the solution is used as a reference substance solution.
(2) Chromatographic conditions:
instrument: shimadzu LC-2030C-PLUS; a detector: UV (ultraviolet) light
Chromatographic column: SYMMETRYSHIELD TM RP18, 4.6X105 mm,5 μm;
mobile phase a: water (phosphoric acid to adjust pH to 2.5);
mobile phase B: acetonitrile
Isocratic elution ratio: mobile phase A-mobile phase B (45:55)
Flow rate: 1.0ml/min;
column temperature: 35 ℃;
detection wavelength: 286nm;
(3) And (3) measuring: and respectively taking 5 mu l of each of the sample solution and the system applicability solution, injecting into a liquid chromatograph, and recording the chromatograms.
Advantageous effects
The chromatographic conditions provided by the invention adopt an isocratic elution mode, so that the separation degree of the main component and photodegradation impurities can be met, the acquisition time is shortened to 20 minutes, and the detection efficiency is improved compared with 50 minutes in the prior art; in addition, the sample is subjected to ultrasonic extraction by adopting methanol before dilution, and the recovery rates of the high concentration, the medium concentration and the low concentration are all about 100%, so that the accuracy is higher.
Drawings
FIG. 1 is a system applicability solution chromatogram under USP chromatographic conditions;
FIG. 2 is a chromatogram of a solution of system applicability under chromatographic conditions of the detection method;
FIG. 3 is a system applicability solution chromatogram under detection method two chromatographic conditions;
FIG. 4 is a solution chromatogram of system applicability under test method triple chromatographic conditions;
FIG. 5 is a diagram of a detection method specificity stack;
FIG. 6 is a linear diagram of a detection method;
Detailed Description
Example 1
The method for detecting the content of the fenofibric acid choline slow-release capsule comprises the following steps:
(1) Preparing a solution:
1L of mobile phase A and 1L of mobile phase B are measured and uniformly mixed to be used as blank solvent;
13mg of fenofibric acid choline raw material is precisely weighed, placed in a 100ml transparent measuring flask, dissolved and diluted to a scale by adding a solvent [ water (pH value is adjusted to 2.5 by phosphoric acid) -acetonitrile (1:1) ] and uniformly shaken. Placing under 5000lx light for 30min, taking out, and taking out to obtain system applicability solution.
(2) Chromatographic conditions:
instrument: shimadzu LC-2030C-PLUS; a detector: UV (ultraviolet) light
Chromatographic column: SYMMETRYSHIELD TM RP18, 4.6X105 mm,5 μm;
mobile phase a: water (phosphoric acid to adjust pH to 2.5);
Mobile phase B: acetonitrile;
Isocratic elution ratio: mobile phase A-mobile phase B (20:80)
Flow rate: 1.0ml/min;
column temperature: 35 ℃;
detection wavelength: 286nm;
(3) And (3) measuring: respectively taking 10 μl of each of the blank solvent and the system applicability solution, injecting into a liquid chromatograph, and recording a chromatogram, wherein a typical chromatogram is shown in fig. 2.
(4) Results and conclusions: compared with fig. 1, the main photodegradation impurity in fig. 2 coincides with the main peak, and the impurity interferes with the determination of the main component, so that the method has poor specificity and needs to be optimized continuously.
Example 2
The second detection method of the content of the fenofibric acid choline slow-release capsule comprises the following steps:
(1) Preparing a solution:
1L of mobile phase A and 1L of mobile phase B are measured and uniformly mixed to be used as blank solvent;
13mg of fenofibric acid choline raw material is precisely weighed, placed in a 100ml transparent measuring flask, dissolved and diluted to a scale by adding a solvent [ water (pH value is adjusted to 2.5 by phosphoric acid) -acetonitrile (1:1) ] and uniformly shaken. Placing under 5000lx light for 30min, taking out, and taking out to obtain system applicability solution.
(2) Chromatographic conditions:
the chromatographic conditions of example 1 were followed except that the isocratic elution ratio was adjusted to mobile phase A-mobile phase B (40:60).
(3) And (3) measuring: respectively taking 10 μl of each of the blank solvent and the system applicability solution, injecting into a liquid chromatograph, and recording a chromatogram, wherein a typical chromatogram is shown in fig. 3.
(4) Results and conclusions: as can be seen from fig. 3, the retention time of the main peak is 9.076min, the separation degree of the main photodegradation impurity from the main peak is 1.647, and the main photodegradation impurity does not reach 2.0 required by pharmacopoeia, so that the main photodegradation impurity has poor specificity, and therefore, the main photodegradation impurity still needs to be optimized continuously.
Example 3
And a third detection method of the content of the fenofibric acid choline slow-release capsule:
(1) Preparing a solution:
1L of mobile phase A and 1L of mobile phase B are measured and uniformly mixed to be used as blank solvent;
13mg of fenofibric acid choline raw material is precisely weighed, placed in a 100ml transparent measuring flask, dissolved and diluted to a scale by adding a solvent [ water (pH value is adjusted to 2.5 by phosphoric acid) -acetonitrile (1:1) ] and uniformly shaken. Placing under 5000lx light for 30min, taking out, and taking out to obtain system applicability solution.
(2) Chromatographic conditions:
The chromatographic conditions of example 1 were followed except that the isocratic elution ratio was adjusted to mobile phase A-mobile phase B (45:55).
(3) And (3) measuring: 5 μl of each of the blank solvent and the system applicability solution was injected into a liquid chromatograph, and a chromatogram was recorded, and a typical diagram is shown in fig. 4.
(4) Results and conclusions: as shown in fig. 4, the retention time of the main peak is 12.214min, the separation degree of the photodegradation impurity and the main peak is 2.938, the separation degree is good, the pharmacopoeia requirements are met, and the specificity requirements are also met. The sample analysis time is greatly shortened compared to fig. 1.
Example 4
Investigation of the extraction mode of the fenofibric acid choline slow-release capsule:
(1) Preparing a solution:
1L of mobile phase A and 1L of mobile phase B are measured and uniformly mixed to be used as blank solvent;
Precisely weighing about 17.87mg of fenofibric acid choline reference substance, placing into a 100ml measuring flask, adding solvent [ water (pH value is adjusted to 2.5 by phosphoric acid) -acetonitrile (1:1) ] to dissolve and dilute to scale, shaking uniformly, and taking as reference substance solution. 2 parts were prepared in parallel.
Precisely weighing 178mg of fenofibric acid choline raw material, placing 138mg of auxiliary materials (prescription components except raw materials) in a 100ml measuring flask, adding 20ml of methanol, preparing 6 samples in parallel, respectively carrying out ultrasonic treatment with 100W ultrasonic power for 10 minutes, 20 minutes and 30 minutes, diluting to scale with a solvent [ water (phosphoric acid is used for adjusting pH value to 2.5) -acetonitrile (1:1) ], shaking uniformly, centrifuging, and taking supernatant; precisely weighing 1ml, placing into a10 ml measuring flask, diluting to scale with solvent [ water (pH value is adjusted to 2.5 by phosphoric acid) -acetonitrile (1:1) ] and shaking uniformly to obtain test solution.
(2) Chromatographic conditions: same as in example 3
(3) And (3) measuring: 5 μl of each of the test solution and the control solution was injected into a liquid chromatograph, and the chromatogram was recorded, and the results are shown in Table 1.
Table 1 extraction method investigation results
(4) Results and conclusions: as can be seen from the results of the sample extraction modes shown in Table 1, the recovery rate is about 100% by adding 20ml of methanol and performing ultrasonic treatment for 10 minutes or more, which indicates that the sample extraction mode is better. Can meet the extraction requirement.
Example 5
Content method specificity investigation of fenofibric acid choline slow-release capsules:
(1) Preparing a solution:
1L of mobile phase A and 1L of mobile phase B are measured and uniformly mixed to be used as blank solvent;
Precisely weighing 137mg of total auxiliary (prescription components except raw materials), placing into a 100ml measuring flask, adding 20ml of methanol, performing ultrasonic treatment for 20 minutes, taking out, shaking, diluting to scale with solvent [ water (pH value is adjusted to 2.5-to acetonitrile (1:1) with phosphoric acid) ] and shaking uniformly. Centrifuging, precisely measuring 1ml of supernatant, placing in a 10ml measuring flask, diluting to scale with solvent, shaking, and taking as blank adjuvant solution.
13.70Mg of fenofibric acid choline raw material is precisely weighed, placed in a 100ml transparent measuring flask, dissolved and diluted to a scale by adding a solvent [ water (pH value is adjusted to 2.5 by phosphoric acid) -acetonitrile (1:1) ] and uniformly shaken. The sample was taken as a system applicability solution by leaving it under 5000lx light for 3 minutes.
Accurately weighing appropriate amounts of the impurities A, E, G, WI-0004 and FNBT, dissolving and diluting the mixture to about 0.2 mug/ml of each impurity in 1ml by adding a solvent [ water (phosphoric acid adjusts pH value to 2.5) -acetonitrile (1:1) ] to obtain a mixed impurity solution.
(2) Chromatographic conditions: same as in example 3
(3) And (3) measuring: and respectively taking 5 mu l of each of the blank solvent, the blank auxiliary material solution, the system applicability solution and the mixed impurity solution, injecting into a liquid chromatograph, and recording a chromatogram, wherein the result is shown in figure 5.
(4) Results and conclusions: the blank solvent, blank auxiliary materials and mixed impurities do not interfere with the determination of fenofibric acid, and the method has good specificity.
Example 6
Linearity and range investigation of fenofibric acid:
(1) Preparing a solution:
1L of mobile phase A and 1L of mobile phase B are measured and uniformly mixed to be used as blank solvent;
Precisely weighing 17.88mg of fenofibric acid choline reference substance, placing into a 10ml brown measuring flask, adding solvent [ water (pH value is adjusted to 2.5 by phosphoric acid) -acetonitrile (1:1) ] to dissolve and dilute to scale, shaking uniformly, and taking as linear mother liquor;
respectively precisely measuring 0.1ml, 0.2ml, 0.5ml, 0.8ml, 1.0ml, 1.2ml, 1.5ml and 2.0ml of linear mother liquor, respectively placing into 10ml measuring flask, diluting to scale with solvent [ water (pH value is adjusted to 2.5 by phosphoric acid) -acetonitrile (1:1) ] and shaking uniformly to obtain linear 10%, 20%, 50%, 80%, 100%, 120%, 150% and 200% concentration solutions.
(2) Chromatographic conditions: same as in example 3
(3) And (3) measuring: the linear solutions with each concentration were taken and injected into a liquid chromatograph at 5. Mu.l each, and the chromatogram was recorded, and the results are shown in FIG. 6.
(4) Results and conclusions: the fenofibric acid is linear within the range of 0.00993mg/ml to 0.1987mg/ml, the linear equation is y= 15365512.1359x-8458.2762, the correlation coefficient r is 0.9999, and the linear correlation is good.
Example 7
Content accuracy investigation of fenofibric acid choline slow-release capsules:
(1) Preparing a solution:
1L of mobile phase A and 1L of mobile phase B are measured and uniformly mixed to be used as blank solvent;
precisely weighing 17.88mg of fenofibric acid choline raw material, placing into a 100ml measuring flask, adding solvent [ water (pH value is adjusted to 2.5 by phosphoric acid) -acetonitrile (1:1) ] to dissolve and dilute to scale, shaking uniformly, and taking as reference substance solution. 2 parts were prepared in parallel.
Precisely weighing 143.05mg of fenofibric acid choline raw material and 137.35mg of total auxiliary materials (prescription components except raw materials), placing into a 100ml measuring flask, adding 20ml of methanol, carrying out ultrasonic treatment for 20min, diluting to scale with solvent [ water (phosphoric acid is used for adjusting pH value to 2.5) -acetonitrile (1:1) ], shaking uniformly, centrifuging, and taking supernatant as 80% of sample solution. 3 parts were prepared in parallel.
Precisely weighing 178.82mg of fenofibric acid choline raw material, carrying out total auxiliary (prescription components except raw materials) 137.35mg, placing into a 100ml measuring flask, adding 20ml of methanol, carrying out ultrasonic treatment for 20min, diluting to scale with solvent [ water (phosphoric acid is used for adjusting pH value to 2.5) -acetonitrile (1:1) ], shaking uniformly, centrifuging, and taking supernatant as 100% of sample solution. 3 parts were prepared in parallel.
Precisely weighing 214.58mg of fenofibric acid choline raw material and 137.35mg of total auxiliary materials (prescription components except raw materials), placing into a 100ml measuring flask, adding 20ml of methanol, performing ultrasonic treatment for 20min, diluting to scale with solvent [ water (phosphoric acid is used for adjusting pH value to 2.5) -acetonitrile (1:1) ], shaking uniformly, centrifuging, and taking supernatant as 120% of sample solution. 3 parts were prepared in parallel.
(2) Chromatographic conditions:
Same as in example 2
(3) And (3) measuring: the blank solvent and 5. Mu.l of each sample solution were measured and injected into the liquid chromatograph, and the chromatogram was recorded, and the results are shown in Table 2.
(4) Results and conclusions: the recovery rate of the product is within the range of 99.27-101.27%, the average recovery rate is 100.3%, the RSD is 0.60%, the recovery rate is good, and the accuracy is high.
TABLE 2 accuracy results
Example 8
Repeated investigation of the content of the fenofibric acid choline slow-release capsule:
(1) Preparing a solution:
1L of mobile phase A and 1L of mobile phase B are measured and uniformly mixed to be used as blank solvent;
precisely weighing 17.88mg of fenofibric acid choline raw material, placing into a 100ml measuring flask, adding solvent [ water (pH value is adjusted to 2.5 by phosphoric acid) -acetonitrile (1:1) ] to dissolve and dilute to scale, shaking uniformly, and taking as reference substance solution. 2 parts were prepared in parallel.
Precisely weighing 178.82mg of fenofibric acid choline raw material, carrying out total auxiliary (prescription components except raw materials) 137.35mg, placing into a 100ml measuring flask, adding 20ml of methanol, carrying out ultrasonic treatment for 20min, diluting to scale with solvent [ water (phosphoric acid is used for adjusting pH value to 2.5) -acetonitrile (1:1) ], shaking uniformly, centrifuging, and taking supernatant as a test sample solution. 6 parts were prepared in parallel.
(2) Chromatographic conditions:
Same as in example 2
(3) And (3) measuring: the blank solvent and 5. Mu.l of each sample solution were measured and injected into the liquid chromatograph, and the chromatogram was recorded, and the results are shown in Table 3.
(4) Results and conclusions: the recovery rate of 6 parts of the sample solution added with the standard is in the range of 100.31-100.97%, the average recovery rate is 100.6%, the RSD is 0.31%, and the repeatability is good.
TABLE 3 repeatability results
Example 9
Content durability investigation of fenofibric acid choline slow-release capsules:
(1) Preparing a solution:
1L of mobile phase A and 1L of mobile phase B are measured and uniformly mixed to be used as blank solvent;
precisely weighing 17.88mg of fenofibric acid choline raw material, placing into a 100ml measuring flask, adding solvent [ water (pH value is adjusted to 2.5 by phosphoric acid) -acetonitrile (1:1) ] to dissolve and dilute to scale, shaking uniformly, and taking as reference substance solution. 2 parts were prepared in parallel.
Precisely weighing 178.82mg of fenofibric acid choline raw material, carrying out total auxiliary (prescription components except raw materials) 137.35mg, placing into a 100ml measuring flask, adding 20ml of methanol, carrying out ultrasonic treatment for 20min, diluting to scale with solvent [ water (phosphoric acid is used for adjusting pH value to 2.5) -acetonitrile (1:1) ], shaking uniformly, centrifuging, and taking supernatant as a test sample solution. 2 parts were prepared in parallel.
(2) Chromatographic conditions:
Same as in example 2
(3) And (3) measuring: the blank solvent and 5. Mu.l of each sample solution were measured and injected into a liquid chromatograph, and the chromatogram was recorded by fine-tuning the column temperature (35.+ -. 5 ℃), the flow rate (1.0.+ -. 0.2 ml/min), and the organic phase ratio (55%.+ -. 2%), and the results are shown in Table 4.
(4) Results and conclusions: the content measuring method has good durability by finely adjusting the column temperature (35 ℃ +/-5 ℃), the flow rate (1.0+/-0.2 ml/min) and the organic phase proportion (55% +/-2%), wherein the content measuring average value under each condition is 99.8%, and the RSD value is 0.49%.
Table 4 content durability test results
Claims (10)
1. The method for detecting the content of the fenofibric acid choline slow-release capsule is characterized by comprising the following steps of:
quantitatively detecting the fenofibric acid choline slow-release capsule by adopting high performance liquid chromatography;
the conditions of high performance liquid chromatography include:
chromatographic column: a chromatographic column using octadecylsilane chemically bonded silica as a filler;
Mobile phase a: water;
mobile phase B: acetonitrile
Flow rate: 1.0+/-0.2 ml/min;
Column temperature: 35+/-5 ℃;
detection wavelength: 286nm;
blank solvent: mobile phase a-mobile phase B;
The system applicability solution is placed for 30 to 50 minutes under 5000 to 7000lx illumination after being prepared; the sample solution is subjected to ultrasonic treatment before dilution.
2. The method for detecting the content of the fenofibric acid choline slow release capsule according to claim 1, wherein the method adopts an isocratic elution mode, and the isocratic elution ratio mobile phase A: mobile phase B was 45:55.
3. The method for detecting the content of the fenofibric acid choline extended release capsule according to claim 1, wherein the system applicability solution is left under 5000lx light for 30min after being prepared.
4. The method for detecting the content of the fenofibric acid choline slow release capsule according to claim 3, wherein the preparation method of the system applicability solution is as follows: precisely weighing 13mg of fenofibric acid choline reference substance, placing into a 100ml transparent measuring flask, adding solvent to dilute to scale, shaking, standing under 5000lx illumination for 30min, and taking out to obtain a system applicability solution; aqueous phosphoric acid in the solvent: the volume of acetonitrile is 1:1, wherein the pH of the water is adjusted to 2.5 by phosphoric acid.
5. The method for detecting the content of the fenofibric acid choline slow release capsule according to claim 1, wherein the ultrasonic treatment time is at least 20 minutes.
6. The method for detecting the content of the fenofibric acid choline slow release capsule according to claim 1, wherein the linear equation is y= 15365512.1359x-8458.2762, and the correlation coefficient r is 0.9999.
7. The method for detecting the content of the fenofibric acid choline slow release capsule according to claim 1, wherein a chromatographic column is adopted: SYMMETRYSHIELD TM RP18, 4.6X250 mm,5 μm.
8. The method for detecting the content of the fenofibric acid choline slow-release capsule according to claim 1, wherein a test solution and a control solution are respectively injected into a liquid chromatograph, a chromatogram is recorded, and the preparation method of the test solution and the control solution is as follows:
Precisely weighing fenofibrate acid choline, placing into a 100ml measuring flask, adding methanol 20ml, performing ultrasonic treatment for 20 min to completely disintegrate, cooling to room temperature, diluting with solvent to scale, shaking, centrifuging, precisely measuring 1ml supernatant, placing into a 10ml measuring flask, diluting with solvent to scale, shaking, and collecting sample solution;
Precisely weighing a fenofibric acid choline reference substance, dissolving with a solvent and diluting to prepare a solution containing 0.13mg of fenofibric acid per 1ml, wherein the solution is used as a reference substance solution; aqueous phosphoric acid in the solvent: the volume of acetonitrile is 1:1, wherein the pH of the water is adjusted to 2.5 by phosphoric acid.
9. The method for detecting the content of the fenofibric acid choline slow-release capsule according to claim 1, wherein the volume ratio of the mobile phase A to the mobile phase B in the blank solvent is 1:1.
10. The method for detecting the content of the fenofibric acid choline slow release capsule according to claim 1, wherein the pH value of water is adjusted to 2.5 by phosphoric acid in a mobile phase A.
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| CN202310366542.XA CN118777441A (en) | 2023-04-07 | 2023-04-07 | Method for detecting content of fenofibric acid choline slow-release capsules |
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