CN116930368A - Detection method of settop alcohol isomer - Google Patents
Detection method of settop alcohol isomer Download PDFInfo
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- CN116930368A CN116930368A CN202310936106.1A CN202310936106A CN116930368A CN 116930368 A CN116930368 A CN 116930368A CN 202310936106 A CN202310936106 A CN 202310936106A CN 116930368 A CN116930368 A CN 116930368A
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- 238000001514 detection method Methods 0.000 title claims abstract description 31
- 150000001298 alcohols Chemical class 0.000 title claims abstract description 10
- ROBLTDOHDSGGDT-UHFFFAOYSA-M sodium;pentane-1-sulfonate Chemical compound [Na+].CCCCCS([O-])(=O)=O ROBLTDOHDSGGDT-UHFFFAOYSA-M 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 23
- 239000007864 aqueous solution Substances 0.000 claims abstract description 16
- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000010829 isocratic elution Methods 0.000 claims abstract description 4
- 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
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- 239000000243 solution Substances 0.000 claims description 19
- 239000002904 solvent Substances 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 abstract description 49
- 239000003814 drug Substances 0.000 abstract description 7
- 238000002360 preparation method Methods 0.000 abstract description 7
- 229940079593 drug Drugs 0.000 abstract description 6
- 238000003908 quality control method Methods 0.000 abstract description 5
- 230000035945 sensitivity Effects 0.000 abstract description 4
- 238000004458 analytical method Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000010828 elution Methods 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 22
- 238000000926 separation method Methods 0.000 description 14
- 238000011835 investigation Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 7
- 239000000523 sample Substances 0.000 description 7
- 238000012937 correction Methods 0.000 description 6
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
- 238000012417 linear regression Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 239000013558 reference substance Substances 0.000 description 2
- 239000012488 sample solution Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003556 anti-epileptic effect Effects 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000007428 synaptic transmission, GABAergic Effects 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
Classifications
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- 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
- G01N30/26—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
- G01N30/62—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
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/027—Liquid chromatography
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of analysis and detection, in particular to a detection method of a settop alcohol isomer. The method adopts high performance liquid chromatography for detection; the chromatographic conditions of the high performance liquid chromatography include: the chromatographic column is octadecylsilane chemically bonded silica chromatographic column; the mobile phase is methanol-0.18 to 0.24 weight percent of sodium pentanesulfonate aqueous solution, and the elution is carried out by adopting an isocratic elution mode; the detector is an ultraviolet detector; the detection wavelength is 260-270 nm; the flow rate is 1.0-1.3 ml/min. The detection method has high sensitivity and good specificity, can detect the cis-isomer of the settop alcohol, can be used for quality control of the settop alcohol raw material and the preparation thereof, and improves the medication safety of the settop alcohol.
Description
Technical Field
The invention relates to the technical field of analysis and detection, in particular to a detection method of a settop alcohol isomer.
Background
Stave is a novel antiepileptic drug which mainly enhances gabaergic neurotransmission by directly acting on neurotransmitter gamma-aminobutyric acid (GABA) receptor, simultaneously inhibits various liver cytochrome P450 enzymes, and increases the blood concentration of part of antiepileptic drugs, thereby exerting antiepileptic effect.
The molecular structure of the settop alcohol contains 1 chiral carbon atom, and a pair of cis-trans isomers exist. In the analysis and detection process of the settop alcohol, the settop alcohol and the settop alcohol are difficult to separate and detect. However, in both the process of drug directed synthesis and the quality control of the final product, it is desirable to control the content of enantiomeric impurities.
At present, the detection method of the stave isomer is not carried in pharmacopoeia of various countries.
Therefore, in the synthesis of the settop alcohol and the preparation process of the preparation, a detection method with high sensitivity and good specificity is established to detect the settop alcohol and the cis-isomer thereof, so that the quality control of the medicine is realized, and the improvement of the medication safety is of great significance.
Disclosure of Invention
Aiming at the technical problems, the invention provides a detection method of a settop alcohol isomer. The detection method has high sensitivity and good specificity, can detect the cis-isomer of the settop alcohol, can be used for quality control of the settop alcohol raw material and the preparation thereof, and improves the medication safety of the settop alcohol.
In order to solve the technical problems, the invention adopts the following technical scheme:
in a first aspect, the invention provides a method for detecting a settop alcohol isomer, which adopts high performance liquid chromatography for detection;
the chromatographic conditions of the high performance liquid chromatography include:
the chromatographic column is octadecylsilane chemically bonded silica chromatographic column;
the mobile phase is sodium pentanesulfonate aqueous solution with methanol of-0.18 wt% -0.24 wt%; the volume ratio of methanol to sodium pentanesulfonate aqueous solution in the mobile phase is (48-58): (52-42) eluting by adopting an isocratic elution mode;
the detector is an ultraviolet detector;
the detection wavelength is 260-270 nm;
the flow rate is 1.0-1.3 ml/min;
the detection method has high sensitivity and good specificity, can detect the cis-isomer of the settop alcohol, can be used for quality control of the settop alcohol raw material and the preparation thereof, and improves the medication safety of the settop alcohol.
The methanol-0.18 to 0.24 weight percent of sodium pentanesulfonate aqueous solution is a mobile phase, and the preparation is simple; the detection method has good separation degree, specificity, accuracy, repeatability, stability and durability, and can ensure stable baseline even if the sample injection amount is large. After the detection, the calculation of the isomer can be performed using a self-control method. In addition, the invention has no special requirement on the chromatographic column, and can save detection cost.
Preferably, the chromatographic column is Agilent C18, specification 4.6X105 mm,3 μm.
Preferably, the volume ratio of methanol to sodium pentanesulfonate aqueous solution in the mobile phase is 53:47, the preferred volume ratio of the mobile phase can lead to higher separation degree between the cis-isomer of the settop alcohol and the cis-isomer of the settop alcohol, thereby achieving the purpose of effectively and accurately detecting the cis-isomer content of the settop alcohol.
Preferably, the detection wavelength is 270nm.
Preferably, the flow rate is 1.2ml/min.
Preferably, the column temperature is 25 to 35 ℃.
Preferably, the solvent of the solution to be tested is a mobile phase.
Preferably, the running time is 30-40 min; the sample injection volume is 8-10 mu l.
Drawings
FIG. 1 is a chromatogram of a blank solvent under the specificity of example 2 of the present invention;
FIG. 2 is a chromatogram of a system applicability solution under specificity in example 2 of the present invention;
FIG. 3 is a linear regression curve of settop alcohol under linear investigation in example 2;
FIG. 4 is a linear regression curve of the cis-isomer under linear investigation in example 2;
FIG. 5 is a chromatogram of the flow rate of 1.1ml/min under the durability test in example 2;
FIG. 6 is a chromatogram of the flow rate of 1.2ml/min under the durability test in example 2;
FIG. 7 is a chromatogram of the flow rate of 1.3ml/min under the durability test in example 2;
fig. 8 shows a volume ratio of 48 in the durability test of example 2: 52 methanol-0.21 wt% sodium pentanesulfonate aqueous solution chromatogram;
fig. 9 shows a volume ratio of 58 in the durability test of example 2: 42 methanol-0.21 wt% sodium pentanesulfonate aqueous solution chromatogram;
FIG. 10 is a column temperature chromatogram at 25℃under the durability test in example 2;
FIG. 11 is a 35℃column temperature chromatogram under the durability test in example 2;
FIG. 12 is a chromatogram of a 0.18wt% aqueous sodium pentanesulfonate solution under the durability test in example 2;
FIG. 13 is a chromatogram of a 0.24wt% aqueous solution of sodium pentanesulfonate under the durability test in example 2.
Detailed Description
The present invention will be described in further detail with reference to specific embodiments in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
Example 1
The embodiment provides a method for detecting a settop alcohol isomer.
Materials and methods:
instrument: high performance liquid chromatograph, ultraviolet detector, measuring flask, electronic balance.
Reagent: methanol, sodium pentanesulfonate, triethylamine, acetonitrile, phosphoric acid, and dimethyl sulfoxide.
Blank solvent: the volume ratio is 53: 47-0.21 wt% sodium pentanesulphonate in water.
1.1 preparation of solution:
system applicability solution: the control of the stavyl alcohol and the control of the cis-isomer of the stavyl alcohol are respectively weighed precisely in proper amounts, dissolved and diluted into each 1ml of mixed solution containing about 1mg of the stavyl alcohol and 10 mug of the cis-isomer of the stavyl alcohol respectively by using a blank solvent, and the mixed solution is used as a system applicability solution.
Test solution: accurately weighing 10mg of setiton, placing in a 10ml measuring flask, dissolving with a blank solvent, diluting to scale, and shaking to obtain the sample solution.
1.2 conditions for high Performance liquid chromatography:
the chromatographic column is Agilent C18, the specification is 4.6X105 mm,3 μm;
the mobile phase is methanol-0.21 wt% sodium pentanesulfonate aqueous solution; volume ratio of methanol and 0.21wt% sodium pentanesulfonate aqueous solution in mobile phase 53:47, eluting by adopting an isocratic elution mode;
the detector is an ultraviolet detector;
the detection wavelength is 270nm;
the flow rate is 1.2ml/min;
the column temperature is 30 ℃;
the sample injection volume is as follows: 10 μl;
the run time was 40min.
Example 2
This example provides a methodological validation of the method for detecting the isomer of settop in example 1.
2.1 specificity
The blank solvent and the system applicability solution of the embodiment 1 are taken to carry out sample injection detection according to the detection conditions of the isomer of the settop alcohol provided in the embodiment 1, the sample injection volume is 10 μl, and a chromatogram is recorded, wherein the chromatogram of the blank solvent is shown in fig. 1. The chromatogram of the system applicability solution is shown in fig. 2.
FIG. 1 is a chromatogram of a blank solvent, showing that the blank solvent does not interfere with the determination of the relevant substances.
FIG. 2 is a chromatogram of a system applicability solution (cis-isomer and settop alcohol in sequence from left to right). From fig. 2, it can be seen that the isomer of settop alcohol is well separated from the settop alcohol, and the isomer of settop alcohol does not interfere with the determination of settop alcohol, indicating that the method has good specificity.
2.2 Linear Range
Precisely weighing a control substance of the settop alcohol and a proper amount of a control substance of the cis isomer of the settop alcohol, and preparing a solution with the following concentration for determination: 0.3. Mu.g/ml, 0.6. Mu.g/ml, 1.2. Mu.g/ml, 3.0. Mu.g/ml, 6.0. Mu.g/ml; the concentration C (. Mu.g/ml) was plotted against the peak area (A) and the results are shown in Table 1, and the linear relationship is shown in FIGS. 3 and 4.
FIG. 3 is a linear regression curve of settop alcohol;
FIG. 4 is a linear regression curve of cis-isomer.
TABLE 1
As can be seen from Table 1, FIG. 3 and FIG. 4, the concentration of the settop alcohol is in the range of 0.297-5.95 mug/ml, the concentration and the peak area are in good linear relation, and the linear equation is: y=40.081x+1.8980, r=0.999; the cis-isomer has a good linear relationship between concentration and peak area in the range of 0.276-5.52 mug/ml, and the linear equation is: y= 42.479x-4.1046, r=0.997.
2.3 correction factors
The cis-isomer correction factor was calculated according to the linear test and the results are shown in Table 2.
TABLE 2 correction factor results
| Name of the name | Linear equation | Correction factor |
| Stave | y＝40.08x+1.890 | — |
| Cis-isomer | y＝42.47x-4.104 | 0.94 |
As is clear from Table 2, the correction factor was 0.94 and was between 0.9 and 1.1, and the measurement was carried out by the self-control method without adding the correction factor.
2.4 accuracy test
Precisely weighing the reference substance of the stavyl alcohol and the reference substance of the cis-isomer of the stavyl alcohol, adding a blank solvent for dissolution, diluting to a scale, and shaking uniformly to prepare the solution of the cis-isomer of the stavyl alcohol containing 1000 mug of the stavyl alcohol and about a certain concentration in each 1ml, wherein the concentrations are in three parts in parallel.
10. Mu.l of each sample solution was precisely measured and injected into a chromatograph, and the measurement was performed under the detection conditions of the isomer of settop alcohol provided in example 1, and the chromatogram was recorded. The results are shown in Table 3.
TABLE 3 cis isomer recovery test results
As can be seen from Table 3, the accuracy of the method is good.
2.5 repeatability test
The precision of the method for determining the cis-isomer of settop alcohol was examined, 6 samples were measured in parallel, and a method reproducibility test was performed.
Six parts of system applicability solution of the cis-isomer of the settop alcohol and the settop alcohol are prepared in parallel, 10 mul of the system applicability solution is precisely measured and injected into a liquid chromatograph, the measurement is carried out according to the detection conditions of the settop alcohol isomer provided in the example 1, a chromatogram is recorded, and the peak area ratio of the cis-isomer to the settop alcohol is taken as an index for investigation. The results are shown in Table 4.
Table 4 repeatability investigation-determination results
| Sample of | 1 | 2 | 3 | 4 | 5 | 6 | RSD(％) |
| Cis-isomer | 0.13 | 0.12 | 0.13 | 0.13 | 0.14 | 0.13 | 4.9 |
As can be seen from Table 4, the results of the measurement of cis-isomer of settop alcohol for six samples tested in parallel are substantially identical, indicating good reproducibility of the process.
2.6 solution stability
The system applicability solution prepared according to 1.1 is placed at room temperature, and is sampled at 0h, 1h, 2h, 3h, 5h and 8h respectively, and is measured according to the detection conditions of the settop alcohol isomer provided in example 1, and a chromatogram is recorded, and peak area is taken as an investigation index. The results are shown in Table 5.
TABLE 5 stability of solution peak areas
| Time (h) | 0 | 1 | 2 | 3 | 5 | 8 | RSD(％) |
| Cis-isomer | 1283.5 | 1298.4 | 1312.3 | 1339.7 | 1275.9 | 1350.9 | 2.3 |
As can be seen from Table 5, the peak area of the cis-isomer does not change significantly within 8 hours at room temperature, indicating that the sample is stable within 8 hours at room temperature.
2.7 durability test
The method can be used for providing basis for routine examination by examining the degree that chromatographic conditions are slightly changed and the result is not affected. The durability investigation of the product is mainly carried out on the chromatographic conditions of the product, such as flow rate, different flow phase proportions, different column temperatures and different chromatographic columns. The method comprises the following steps:
(1) Investigation of different flow rates
The flow rate of the product was set to 1.2ml/min by conventional operation, and now the flow rates were adjusted to 1.3ml/min and 1.1ml/min, respectively, and the durability of the product under different flow rate conditions was examined, and the results are shown in Table 6.
TABLE 6 durability-different flow rates (degree of separation of settop alcohol from its cis isomer)
| Flow rate (ml/min) | 1.1 | 1.2 | 1.3 |
| Degree of separation | 1.91 | 1.74 | 2.0 |
Chromatograms of different flow rates are shown in fig. 5-7.
FIG. 5 is a chromatogram of a flow rate of 1.1ml/min under durability test;
FIG. 6 is a chromatogram of a flow rate of 1.2ml/min under durability test;
FIG. 7 is a chromatogram of a flow rate of 1.3ml/min under durability test;
as can be seen from Table 6 and FIGS. 5 to 7, the separation degree of the cis-isomer (each impurity) of the stave main drug and the stave reaches 1.5 under the condition of different flow rates, which meets the requirements.
(2) Investigation of different mobile phase proportions
The mobile phase of the product is a mobile phase of aqueous solution of sodium pentanesulfonate with the volume ratio of 53:47 of methanol to 0.21wt percent, and the volume ratio of the mobile phase is adjusted to be 48:52 and 58: 42-0.21 wt% sodium pentanesulphonate in water, and the results are shown in Table 7.
TABLE 7 durability-different flow phase ratios (degree of separation)
The different mobile phase ratio chromatograms are shown in fig. 8-9.
Fig. 8 shows a volume ratio of 48 in the durability test: 52 methanol-0.21 wt% sodium pentanesulfonate aqueous solution chromatogram;
FIG. 9 is a chromatogram of a methanol-0.21 wt% sodium pentanesulfonate aqueous solution at a volume ratio of 58:42 for durability testing;
as can be seen from Table 7 and FIGS. 8-9, the separation degree of the cis-isomer of the settop alcohol and the settop alcohol can meet the requirements by slightly changing the proportion of the mobile phase.
(3) Investigation of different column temperatures
The column temperature of the product is 30 ℃ according to the conventional operation, the column temperature is now respectively adjusted to 25 ℃ and 35 ℃, and the durability of the product under different column temperature conditions is examined, and the results are shown in Table 8.
TABLE 8 durability-different column temperatures (degree of separation)
| Column temperature (. Degree. C.) | 25 | 30 | 35 |
| Degree of separation | 1.93 | 1.74 | 1.81 |
Chromatograms at different column temperatures are shown in fig. 10-11.
FIG. 10 is a 25℃column temperature chromatogram under durability test;
FIG. 11 is a 35℃column temperature chromatogram under durability test;
as can be seen from Table 7 and FIGS. 10-11, the separation degree of the settop alcohol and the cis-isomer thereof reaches 1.5 under different column temperature conditions, which meets the requirements.
(4) Different sodium pentanesulphonate concentration
The volume ratio of 0.18wt% and 0.24wt% sodium pentanesulphonate solution to methanol was examined to be 47: the effect on the cis-isomer of settop and the degree of separation of settop at 53 is shown in Table 9.
TABLE 9 durability-sodium pentanesulfonate concentration (degree of separation)
| Sodium pentanesulphonate concentration | 0.18wt％ | 0.21wt％ | 0.24wt％ |
| Degree of separation | 2.19 | 1.74 | 2.16 |
Chromatograms at different sodium pentanesulphonate concentrations are shown in figures 12-13.
As can be seen from Table 9 and FIGS. 12-13, both the cis-isomer of the settop alcohol and the degree of separation of the settop alcohol met the requirements with small changes in the concentration of sodium pentanesulfonate.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, or alternatives falling within the spirit and principles of the invention.
Claims (8)
1. A detection method of a settop alcohol isomer is characterized in that high performance liquid chromatography is adopted for detection;
the chromatographic conditions of the high performance liquid chromatography include:
the chromatographic column is octadecylsilane chemically bonded silica chromatographic column;
the mobile phase is sodium pentanesulfonate aqueous solution with methanol of-0.18 wt% -0.24 wt%; the volume ratio of methanol to sodium pentanesulfonate aqueous solution in the mobile phase is (48-58): (52-42) eluting by adopting an isocratic elution mode;
the detector is an ultraviolet detector;
the detection wavelength is 260-270 nm;
the flow rate is 1.0-1.3 ml/min.
2. The method according to claim 1, wherein the chromatographic column is Agilent C18, with a specification of 4.6x150mm, 3 μm.
3. The method according to claim 1, wherein the mobile phase is methanol-0.21 wt% aqueous sodium pentanesulfonate; the volume ratio of the methanol to the sodium pentanesulfonate aqueous solution is 53:47.
4. the method according to claim 1, wherein the detection wavelength is 270nm.
5. The method of claim 1, wherein the flow rate is 1.2ml/min.
6. The method according to claim 1, wherein the column temperature is 25 to 35 ℃.
7. The method according to claim 1, wherein the solvent of the solution to be tested is a mobile phase.
8. The method according to claim 1, wherein the sample volume is 8 to 10. Mu.l.
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| US20210052547A1 (en) * | 2016-02-15 | 2021-02-25 | Institut National De La Sante Et De La Recherche Medicale (Nserm) | Use of stiripentol and their derivatives for decreasing urinary oxalate concentration in an individual |
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| CN111943928A (en) * | 2020-08-21 | 2020-11-17 | 石家庄四药有限公司 | Synthesis method and application of stiripentol intermediate impurity and stiripentol impurity |
| CN114544796A (en) * | 2021-12-15 | 2022-05-27 | 安徽万邦医药科技股份有限公司 | Method for determining stiripentol in plasma by liquid-phase mass spectrometry |
| CN116350592A (en) * | 2023-03-22 | 2023-06-30 | 中南民族大学 | Setitol nanocrystalline and preparation method and application thereof |
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