CN112433016A - Liquid chromatography analysis method for detecting content of rearranged ester - Google Patents
Liquid chromatography analysis method for detecting content of rearranged ester Download PDFInfo
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- 150000002148 esters Chemical class 0.000 title claims abstract description 77
- 238000004811 liquid chromatography Methods 0.000 title claims abstract description 28
- 238000004458 analytical method Methods 0.000 title claims abstract description 22
- 239000002994 raw material Substances 0.000 claims abstract description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 24
- 238000001514 detection method Methods 0.000 claims abstract description 17
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims abstract description 8
- 230000008707 rearrangement Effects 0.000 claims abstract description 6
- PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000000523 sample Substances 0.000 claims description 45
- 239000007788 liquid Substances 0.000 claims description 27
- 239000012488 sample solution Substances 0.000 claims description 22
- 239000012086 standard solution Substances 0.000 claims description 14
- 239000000126 substance Substances 0.000 claims description 13
- 239000000243 solution Substances 0.000 claims description 7
- 238000005303 weighing Methods 0.000 claims description 4
- 230000003247 decreasing effect Effects 0.000 claims description 3
- 230000014759 maintenance of location Effects 0.000 claims description 3
- 238000004445 quantitative analysis Methods 0.000 abstract description 4
- GJSDKKUJJNIQQV-UHFFFAOYSA-N (3-chloro-2,2-dimethylpropyl) 2-[4-(2-methylpropyl)phenyl]propanoate Chemical compound CC(C)CC1=CC=C(C(C)C(=O)OCC(C)(C)CCl)C=C1 GJSDKKUJJNIQQV-UHFFFAOYSA-N 0.000 abstract description 2
- 238000010812 external standard method Methods 0.000 abstract description 2
- 239000012071 phase Substances 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 6
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 5
- 229960001680 ibuprofen Drugs 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- SLCVBVWXLSEKPL-UHFFFAOYSA-N neopentyl glycol Chemical compound OCC(C)(C)CO SLCVBVWXLSEKPL-UHFFFAOYSA-N 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000002835 absorbance Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 238000010606 normalization Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 238000003908 quality control method Methods 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 2
- XENVCRGQTABGKY-ZHACJKMWSA-N chlorohydrin Chemical compound CC#CC#CC#CC#C\C=C\C(Cl)CO XENVCRGQTABGKY-ZHACJKMWSA-N 0.000 description 2
- 238000006266 etherification reaction Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- PTTPUWGBPLLBKW-UHFFFAOYSA-M sodium;2-[4-(2-methylpropyl)phenyl]propanoate Chemical compound [Na+].CC(C)CC1=CC=C(C(C)C([O-])=O)C=C1 PTTPUWGBPLLBKW-UHFFFAOYSA-M 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- JEQDSBVHLKBEIZ-REOHCLBHSA-N (2s)-2-chloropropanoyl chloride Chemical compound C[C@H](Cl)C(Cl)=O JEQDSBVHLKBEIZ-REOHCLBHSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 231100000024 genotoxic Toxicity 0.000 description 1
- 230000001738 genotoxic effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- KXUHSQYYJYAXGZ-UHFFFAOYSA-N isobutylbenzene Chemical compound CC(C)CC1=CC=CC=C1 KXUHSQYYJYAXGZ-UHFFFAOYSA-N 0.000 description 1
- 238000005907 ketalization reaction Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
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Classifications
-
- 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
- G01N30/02—Column chromatography
-
- 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
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- 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
- 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
-
- 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
- G01N30/02—Column chromatography
- G01N30/60—Construction of the column
-
- 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
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
-
- 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
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N2030/042—Standards
- G01N2030/047—Standards external
Abstract
The invention discloses a liquid chromatography analysis method of rearrangement ester (II, alpha-methyl-4- (2-methylpropyl) phenylacetic acid-3-chloro-2, 2-dimethylpropyl ester), which comprises the steps of sample preparation analysis, liquid chromatography analysis conditions and qualitative and quantitative methods; the liquid chromatography conditions were: a) mobile phase: a first raw material: acetonitrile or methanol; the second raw material is 1% phosphoric acid or acetic acid water solution; b) mobile phase ratio first feedstock to second feedstock =80: 20; c) sample introduction volume: 20.0 muL; d) column oven: 30 ℃; e) flow rate: 1 mL/min; f) detection type: an ultraviolet detector; g) detection wavelength: 222 nm; h) a chromatographic column: c18, 150mm × 4.6mm × 2.6 μm; the residence time of the rearranged ester was 6.925 min; the quantitative method used is an external standard method. The method has simple operation and low cost, and can quickly, efficiently and accurately analyze the rearranged ester.
Description
Technical Field
The invention relates to the technical field of pharmacy, in particular to a liquid chromatography analysis method for detecting the content of rearranged ester.
Background
Ibuprofen is used as an effective nonsteroidal anti-inflammatory analgesic, and the production process of the ibuprofen is generally an aryl 1, 2-transposition rearrangement method adopted in China at present, wherein the ibuprofen is prepared by taking isobutylbenzene as a raw material and carrying out the steps of parack acylation with 2-chloropropionyl chloride, catalytic ketalization with neopentyl glycol, catalytic rearrangement, hydrolysis, acidification and the like. The hydrolysis reaction in the process is that rearranged ester with a certain concentration reacts with sodium hydroxide to generate ibuprofen sodium salt and chlorohydrin, the ibuprofen sodium salt is acidified to obtain ibuprofen, meanwhile, byproduct chlorohydrin can be subjected to etherification reaction at 75 ℃ in an alkaline environment, neopentyl glycol can be prepared by acid hydrolysis after etherification ring formation, neopentyl glycol can be prepared by concentration and then applied to condensation reaction, the consumption of industrial neopentyl glycol can be greatly reduced, raw materials and cost are saved, and meanwhile, the material recycling also meets the requirement of green chemistry. The rearranged ester (II, alpha-methyl-4- (2-methylpropyl) phenylacetic acid-3-chloro-2, 2-dimethylpropyl ester) is an intermediate in the method, called rearranged ester (II) for short, the rearranged ester is used as a chloride, is suspected genotoxic impurity, and the residue of the rearranged ester needs to be strictly controlled in an ibuprofen finished product.
At present, for the determination of the content of the rearranged ester, a liquid chromatogram area normalization method is used in most documents, the chromatographic column conditions are not clear, the product impurities are complex in actual production, and the difference of response factors among components in the liquid chromatogram is large, so that the content of the rearranged ester cannot be accurately determined by simply using the area normalization method, and the influence on the production process is large.
Disclosure of Invention
The invention aims to provide a rapid, efficient and accurate analysis method for rearranged ester, which is used for solving the technical problems that the chromatographic conditions are not clear due to the fact that a liquid chromatogram area normalization method is used for detecting the content of the rearranged ester at present, and the difference of response factors in liquid chromatogram among all components is large due to the fact that product impurities are complex in actual production.
In order to achieve the above object, the present invention provides a liquid chromatography method for detecting a content of a rearranged ester, comprising the steps of:
s1, preparing a sample solution to be detected, namely adding a sample to be detected containing the rearrangement ester into the mobile phase for dissolving to prepare the sample solution to be detected;
s2, carrying out chromatographic detection on the sample solution to be detected, namely injecting the sample solution to be detected into a liquid chromatograph, carrying out chromatographic detection, and determining the quality by retention time to obtain the content of the rearranged ester;
and S3, calculating the content of the sample to be detected, and calculating to obtain the content of the rearranged ester in the sample to be detected according to the standard curve.
Further, the concentration of the sample to be detected in the sample solution to be detected is (1-20) g/L.
Further, the mobile phase comprises a first raw material and a second raw material, wherein the ratio of the first raw material to the second raw material is 4:1-3: 1; the first raw material is acetonitrile or methanol, and the second raw material is 1% phosphoric acid or acetic acid water solution.
Further, the step S1 of configuring a sample solution to be tested specifically includes: taking 0.1g-2g of a sample to be detected, placing the sample to be detected in a 100mL volumetric flask, and uniformly preparing the sample solution to be detected by using a mobile phase constant volume shaker.
Further, the step S3 of calculating the content of the sample to be tested specifically includes:
s31, preparing standard solutions with different concentration gradients, namely taking a rearranged ester standard substance, dividing the rearranged ester standard substance into a plurality of parts according to the sequence of increasing or decreasing the weight in sequence, and preparing the rearranged ester standard substance into a plurality of parts of standard solutions with different concentration gradients by constant volume shaking of a mobile phase;
and S32, drawing a standard curve, namely respectively injecting a certain amount of standard solution into a liquid chromatograph, taking the peak area of the rearranged ester standard product as a vertical coordinate and the weight of the rearranged ester standard product as a horizontal coordinate according to a chromatogram, and preparing the standard curve.
Further, the step S31 of configuring standard solutions with different concentration gradients specifically includes: weighing 0.0050g, 0.0075g, 0.0100g, 0.0150g and 0.0200g of rearranged ester standard substance respectively, placing in a 100mL volumetric flask, and using a mobile phase to fix the volume and uniformly shake to prepare a plurality of standard solutions with different concentration gradients.
Further, the chromatographic conditions of the liquid chromatograph are as follows:
a) mobile phase: a first raw material: acetonitrile or methanol; the second raw material is 1% phosphoric acid or acetic acid water solution
b) The ratio of the first raw material to the second raw material is 80: 20;
c) sample introduction volume: 20.0 mu L;
d) column oven: 30 ℃;
e) flow rate: 1 mL/min;
f) detection type: an ultraviolet detector;
g) detection wavelength: 222 nm;
h) a chromatographic column: c18 liquid chromatography column, 150mm × 4.6mm × 2.6 μm;
further, the liquid chromatograph is an ultraviolet detector.
Further, the liquid chromatograph includes a chromatography column.
Further, the column was a C18 liquid chromatography column having a specification of 150mm × 4.6mm × 2.6 μm.
The method has the advantages that the method uses a liquid chromatograph, selects a chromatographic column with the size of C18 and the size of 150mm multiplied by 4.6mm multiplied by 2.6 mu m, can obtain better peak effect, has wider linear range and shorter analysis time, and is suitable for analyzing the rearranged ester samples with different unknown concentrations; meanwhile, considering that some impurities which can not generate peaks under the condition of liquid chromatography exist in the sample, the external standard method is particularly adopted for quantitative analysis, the technical blank of the corresponding field is filled, and the method has the advantages of simplicity, rapidness, stability, good chromatographic peak shape, high accuracy, good reproducibility and the like, and has important practical significance in the fields of quality analysis, quality control and the like of the rearranged ester.
Drawings
The technical solution and other advantages of the present application will become apparent from the detailed description of the embodiments of the present application with reference to the accompanying drawings.
FIG. 1 is a flow chart of a liquid chromatography method for detecting the content of a rearranged ester according to an embodiment of the present invention;
FIG. 2 is an analytical spectrum of a rearranged ester standard;
FIG. 3 is an analytical spectrum of example 1;
FIG. 4 is an analytical spectrum of example 2.
Detailed Description
The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. It is to be understood that the embodiments described are only a few 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.
As shown in fig. 1, an embodiment of the present invention provides a liquid chromatography method for detecting a content of a rearranged ester, which includes steps S1-S3.
S1, preparing a sample solution to be detected, namely dissolving the sample to be detected containing the rearranged ester to prepare the sample solution to be detected.
The step S1 of preparing a sample solution to be tested specifically includes: taking 0.1g-2g of a sample to be detected, placing the sample to be detected in a 100mL volumetric flask, and uniformly preparing the sample solution to be detected by using a mobile phase constant volume shaker.
Wherein the concentration of the sample to be detected in the sample solution to be detected is (1-20) g/L. The mobile phase comprises a first raw material A and a second raw material B, and the ratio of the first raw material A to the second raw material B is 4:1-3: 1; the first raw material A is acetonitrile or methanol, and the second raw material B is 1% phosphoric acid or acetic acid aqueous solution.
S2, carrying out chromatographic detection on the sample solution to be detected, namely injecting the sample solution to be detected into a liquid chromatograph, carrying out chromatographic detection, and determining the quality by retention time to obtain the content of the rearranged ester.
And S3, calculating the content of the sample to be detected, and calculating to obtain the content of the rearranged ester in the sample to be detected according to the standard curve.
The step S3 of calculating the content of the sample to be detected specifically comprises S31-S32.
S31, preparing standard solutions with different concentration gradients, namely taking a rearranged ester standard substance, dividing the rearranged ester standard substance into a plurality of parts according to the sequence of increasing or decreasing the weight in sequence, and preparing the rearranged ester standard substance into a plurality of parts of standard solutions with different concentration gradients by constant volume shaking of a mobile phase. The step S31 of preparing standard solutions with different concentration gradients specifically includes: weighing 0.0050g, 0.0075g, 0.0100g, 0.0150g and 0.0200g of rearranged ester standard substance respectively, placing in a 100mL volumetric flask, and using a mobile phase to fix the volume and uniformly shake to prepare a plurality of standard solutions with different concentration gradients.
And S32, drawing a standard curve, namely injecting a certain amount of standard liquid into a chromatographic column and injecting the standard liquid into a liquid chromatograph, taking the peak area ratio of the rearranged ester standard product as a vertical coordinate and the weight of the rearranged ester standard product as a horizontal coordinate according to a chromatogram, and preparing the standard curve.
Further, the chromatographic conditions of the liquid chromatograph are as follows:
a) mobile phase: a: acetonitrile or methanol; b1% phosphoric acid or acetic acid aqueous solution
b) The ratio of mobile phase A to B is 80 to 20;
c) sample introduction volume: 20.0 mu L;
d) column oven: 30 ℃;
e) flow rate: 1 mL/min;
f) detection type: an ultraviolet detector;
g) detection wavelength: 222 nm;
h) a chromatographic column: c18 liquid chromatography column, 150mm × 4.6mm × 2.6 μm;
further, the liquid chromatograph is an ultraviolet detector.
Further, the liquid chromatograph includes a chromatography column.
Further, the column was a C18 liquid chromatography column having a specification of 150mm × 4.6mm × 2.6 μm.
According to the method for quantitatively analyzing the rearranged ester by using the liquid chromatography, the used liquid chromatograph selects a chromatographic column with the size of C18 and the size of 150mm multiplied by 4.6mm multiplied by 2.6 mu m, so that a better peak effect can be obtained, the linear range is wider, the analysis time is shorter, and the method is suitable for analyzing the rearranged ester samples with different unknown concentrations; meanwhile, the method considers that some impurities which can not generate peaks under the liquid chromatogram condition exist in the sample, fills up the technical blank in the corresponding field, has the advantages of simplicity, rapidness, stability, good chromatographic peak shape, high accuracy, good reproducibility and the like, and has important practical significance in the fields of quality analysis, quality control and the like of the rearranged ester.
The following examples are given for illustration, and it is noted that the production of the rearranged ester can be carried out in practice by expanding the proportion of the same according to the contents of the following examples.
Example 1
1.1 reagents and instruments
Methanol: HPLC;
rearrangement ester standard sample: the self-made purity is 98.9%;
analytical balance: 0.0001 g;
organic phase microporous filter membrane: 0.22 μm;
liquid chromatograph: u3000, Sammer Feisha, Inc., ultraviolet detector, configuration
An autosampler;
capillary chromatographic column: c18 liquid chromatography column, 150mm × 4.6mm × 2.6 μm, Saimer
An airline company;
1.2 chromatographic methods
a) Mobile phase: a: acetonitrile or methanol; b1% phosphoric acid or acetic acid aqueous solution
b) The ratio of mobile phase A to B is 80 to 20;
c) sample introduction volume: 20.0 mu L;
d) column oven: 30 ℃;
e) flow rate: 1 mL/min;
f) detection type: an ultraviolet detector;
g) detection wavelength: 222 nm;
h) a chromatographic column: c18 liquid chromatography column, 150mm × 4.6mm × 2.6 μm;
1.3 drawing a standard curve
The standard working solutions were separately collected and subjected to chromatographic analysis under the chromatographic conditions of 1.2.
And drawing a standard curve according to the corresponding relation between the peak area of the sample measured at each concentration in the concentration gradient and the weight of the standard sample, wherein the obtained standard curve y is 0.2338x-0.00002, and the regression coefficient is 0.9999.
1.4 measurement and calculation of samples
Taking a sample in a hydrolysis process stage, heating the sample in the stage to ensure the uniformity of the sample, wherein the sample contains about 33% of salt substances in rearranged ester, sampling while the sample is hot, accurately weighing 1.0025g of the sample into a 100mL volumetric flask, adding a mobile phase to a constant volume, shaking uniformly, filtering by using a 0.22 mu m filter membrane, and then carrying out sample injection analysis.
The analytical spectrum of the rearranged ester is shown in FIG. 3, in which the residence time of the rearranged ester is 6.925min, and the content of the rearranged ester is 0.0543% according to the standard curve.
1.5 method repeatability
Precisely measuring the sample solution, injecting into a liquid chromatograph for detection, continuously detecting for 5 times, and calculating the Relative Standard Deviation (RSD) of the content, wherein the results are shown in Table 1. Table 1 shows the relative standard deviations of the rearranged esters in this example.
| Sample | Content% | |
| 1 | 0.0538 | |
| 2 | 0.0547 | |
| 3 | 0.0550 | |
| 4 | 0.0539 | |
| 5 | 0.0542 | |
| Average value% | 0.05432 | |
| RSD％ | 0.95 |
TABLE 1
1.6 accuracy test
Different amounts of the rearranged ester standards were added to example sample 1 and quantitatively analyzed under the same chromatographic conditions to calculate the recovery of the added standards, as shown in table 2. Table 2 shows the normalized recovery of the rearranged ester of this example.
| Sample (I) | Example 1 sample size | Added in an amount of g | Detected amount g | The recovery rate is high |
| 1 | 1.0125 | 0.0005 | 0.000485 | 97.00 |
| 2 | 1.0825 | 0.0005 | 0.000497 | 99.40 |
TABLE 2
In conclusion, the residence time of the rearranged ester was 6.925 min; the quantitative method used is an external standard curve method. The method has simple operation and low cost, and can quickly, efficiently and accurately analyze the rearranged ester.
Example 2
Example 2 includes most of the technical features of example 1, and differs from example 1 in that the sampling position in example 2 is the raw material of the hydrolysis process in production, about 70% of the material is rearranged ester, so the pretreatment mode is as follows: 1.0258g of sample is taken and put into a 100mL volumetric flask, mobile phase constant volume is added and shaken up to be used as sample stock solution, then 1mL of sample stock solution is added into the 100mL volumetric flask and diluted by the mobile phase constant volume, and the sample is filtered by a 0.22 mu m filter membrane and then injected for analysis.
The analytical chromatogram of this example is shown in FIG. 4, and the content of the rearranged ester is calculated according to the present method to be 69.511%.
Wherein the Absorbance or Absorbance is shown on the vertical axis in FIGS. 2 to 4, and is shown by Absorbance in FIGS. 2 to 4.
Therefore, the method can be suitable for analyzing the rearranged ester samples with different unknown concentrations, can realize better peak-generating effect, and has wider linear range; fills up the technical blank in the corresponding field, has the advantages of simplicity, rapidness, stability, good chromatographic peak shape, high accuracy, good reproducibility and the like, and has important practical significance in the fields of quality analysis, quality control and the like of the rearranged ester.
In the foregoing embodiments, the descriptions of the respective embodiments have respective emphasis, and for parts that are not described in detail in a certain embodiment, reference may be made to related descriptions of other embodiments. The liquid chromatography analysis method for detecting the content of the rearranged ester provided by the embodiment of the application is described in detail, the principle and the implementation mode of the application are explained by applying specific examples, and the description of the embodiment is only used for helping to understand the technical scheme and the core idea of the application; those of ordinary skill in the art will understand that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; such modifications or substitutions do not depart from the spirit and scope of the present disclosure as defined by the appended claims.
Claims (10)
1. A liquid chromatography method for detecting the content of rearranged ester is characterized by comprising the following steps:
s1, preparing a sample solution to be detected, namely adding a sample to be detected containing the rearrangement ester into the mobile phase for dissolving to prepare the sample solution to be detected;
s2, carrying out chromatographic detection on the sample solution to be detected, namely injecting the sample solution to be detected into a liquid chromatograph, carrying out chromatographic detection, and determining the quality by retention time to obtain the content of the rearranged ester;
and S3, calculating the content of the sample to be detected, and calculating to obtain the content of the rearranged ester in the sample to be detected according to the standard curve.
2. The liquid chromatography analysis method for detecting the content of a rearranged ester according to claim 1, wherein the concentration of the sample to be tested in the sample solution to be tested is (1-20) g/L.
3. The liquid chromatography analysis method for detecting the content of the rearranged ester according to claim 1, wherein the mobile phase comprises a first raw material and a second raw material, and the ratio of the first raw material to the second raw material is 4:1-3: 1; the first raw material is acetonitrile or methanol, and the second raw material is 1% phosphoric acid or acetic acid water solution.
4. The method for liquid chromatography analysis of rearranged ester content according to claim 1, wherein the step S1 of configuring a sample solution to be tested specifically comprises:
taking 0.1g-2.0g of a sample to be detected, placing the sample to be detected in a 100mL volumetric flask, and uniformly preparing the sample solution to be detected by using a mobile phase constant volume shaker.
5. The liquid chromatography analysis method for detecting the content of the rearranged ester according to claim 1, wherein the step S3 of calculating the content of the sample to be detected specifically comprises:
s31, preparing standard solutions with different concentration gradients, namely taking a rearranged ester standard substance, dividing the rearranged ester standard substance into a plurality of parts according to the sequence of increasing or decreasing the weight in sequence, and uniformly shaking the rearranged ester standard substance by using flow compatibility to prepare a plurality of parts of standard solutions with different concentration gradients;
and S32, drawing a standard curve, namely respectively injecting a certain amount of standard solution into a liquid chromatograph, taking the peak area value of the rearranged ester standard product as a vertical coordinate and the weight of the rearranged ester standard product as a horizontal coordinate according to a chromatogram, and preparing the standard curve.
6. The method for liquid chromatography analysis of rearranged ester content according to claim 4, wherein the step S31 of configuring standard solutions with different concentration gradients specifically comprises:
weighing 0.0050g, 0.0075g, 0.0100g, 0.0150g and 0.0200g of rearranged ester standard substance respectively, placing in a 100mL volumetric flask, and using a mobile phase to fix the volume and uniformly shake to prepare a plurality of standard solutions with different concentration gradients.
7. The liquid chromatography analysis method for detecting a content of a rearranged ester according to claim 1, wherein the chromatographic conditions of the liquid chromatograph are:
a) mobile phase: a first raw material: acetonitrile or methanol; the second raw material is 1% phosphoric acid or acetic acid water solution;
b) mobile phase ratio first feedstock to second feedstock =80: 20;
c) sample introduction volume: 20.0 muL;
d) column oven: 30 ℃;
e) flow rate: 1 mL/min;
f) detection type: an ultraviolet detector;
g) detection wavelength: 222 nm;
h) a chromatographic column: c18 liquid chromatography column, 150mm × 4.6mm × 2.6 μm.
8. The method for liquid chromatography analysis for detecting a content of a rearranged ester according to claim 1 or 4, wherein the liquid chromatograph is an ultraviolet detector.
9. The liquid chromatography method for detecting a content of a rearranged ester according to claim 1, wherein the liquid chromatograph includes a chromatographic column.
10. The method of claim 9, wherein the chromatographic column is a C18 liquid chromatographic column having a specification of 150mm x 4.6mm x 2.6 μm.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5151551A (en) * | 1990-09-06 | 1992-09-29 | Hoechst Celanese Corporation | Method for purification of ibuprofen comprising mixtures |
| CN106940355A (en) * | 2017-04-24 | 2017-07-11 | 中国药科大学 | A kind of detection method of brufen, its sodium salt and its preparation about material |
| CN110068633A (en) * | 2019-05-24 | 2019-07-30 | 山东新华制药股份有限公司 | The liquid chromatography detecting method of caution structure substance in a kind of brufen |
| CN110590546A (en) * | 2019-09-24 | 2019-12-20 | 山东新华制药股份有限公司 | Method for controlling rearrangement ester in ibuprofen preparation process |
-
2020
- 2020-12-11 CN CN202011439554.3A patent/CN112433016A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5151551A (en) * | 1990-09-06 | 1992-09-29 | Hoechst Celanese Corporation | Method for purification of ibuprofen comprising mixtures |
| CN106940355A (en) * | 2017-04-24 | 2017-07-11 | 中国药科大学 | A kind of detection method of brufen, its sodium salt and its preparation about material |
| CN110068633A (en) * | 2019-05-24 | 2019-07-30 | 山东新华制药股份有限公司 | The liquid chromatography detecting method of caution structure substance in a kind of brufen |
| CN110590546A (en) * | 2019-09-24 | 2019-12-20 | 山东新华制药股份有限公司 | Method for controlling rearrangement ester in ibuprofen preparation process |
Non-Patent Citations (3)
| Title |
|---|
| DAVID R.SNEAD 等: "A Three-Minute Synthesis and Purification of Ibuprofen:Pushing the Limits of Continuous-Flow Processing", 《ANGEW.CHEM.INT.ED.》 * |
| 刘忠 等: "高效液相色谱法测定布洛芬注射液的含量及有关物质", 《中国医院药学杂志》 * |
| 张秉华 等: "布洛芬原料及制剂有关物质的研究", 《中国药学杂志》 * |
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