CN113640408B - Method for analyzing piperidinol compound - Google Patents
Method for analyzing piperidinol compound Download PDFInfo
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- CN113640408B CN113640408B CN202110859211.0A CN202110859211A CN113640408B CN 113640408 B CN113640408 B CN 113640408B CN 202110859211 A CN202110859211 A CN 202110859211A CN 113640408 B CN113640408 B CN 113640408B
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- hollow fiber
- piperidinol
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- benzyl
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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
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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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
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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
- G01N30/86—Signal analysis
- G01N30/8675—Evaluation, i.e. decoding of the signal into analytical information
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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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
- G01N2030/062—Preparation extracting sample from raw material
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- 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
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/54—Improvements relating to the production of bulk chemicals using solvents, e.g. supercritical solvents or ionic liquids
Abstract
Disclosed is an analytical method for a piperidinol compound, which is selected from a hollow fiber liquid-phase microextraction and liquid chromatography combined analytical method. Compared with the conventional liquid chromatography, the method can realize the enrichment of 1-benzyl-3-piperidinol, the enrichment multiple is as high as tens of times, and the detection limit is obviously reduced, so that the sensitivity of the analysis method is improved.
Description
Technical Field
The invention belongs to the technical field of analytical chemistry; relates to a method for analyzing a piperidinol compound; in particular to an analysis method combining hollow fiber liquid phase micro-extraction and liquid chromatography.
Background
1-benzyl-3-piperidinol is a key intermediate of Benidipine (Benidipine), which can be obtained from it by a one-step esterification reaction. Benidipine has the effects of reducing blood pressure, resisting angina and protecting kidney, and has certain influence on bone metabolism. Benidipine is a second generation dihydropyridine calcium antagonist drug, has stronger action effect than nifedipine and amlodipine, and has good protective function on blood vessels. In the synthesis process, the used intermediate 1-benzyl-3-piperidinol is (R) -1-benzyl-3-piperidinol.
For the detection analysis of 1-benzyl-3-piperidinol, a liquid chromatography analysis method is generally adopted. Before analysis, selecting proper chromatographic column and mobile phase, flushing the chromatographic column after the pump is started, injecting a sample into an injection port by using a micro-injector after the chromatographic column reaches balance and a base line is balanced, and carrying the sample into the chromatographic column by the mobile phase for separation. The separated components flow into a flow cell of a detector in sequence and are finally discharged into an effluent collector together with the eluent. When a sample component flows through the flow cell, the detector converts the component concentration into an electrical signal, which is amplified and recorded by a recorder to obtain a chromatogram.
With the continuous development of the technology, new technologies for sample pretreatment continuously appear, such as a solid phase extraction technology, a membrane extraction technology, a supercritical fluid extraction technology, a microwave-assisted extraction technology, an ultrasonic extraction technology and the like. These sample pretreatment techniques successfully overcome some of the disadvantages of conventional methods.
However, when the concentration of 1-benzyl-3-piperidinol in water is low, the detection limit of the instrument is so far apart that the qualitative and quantitative analysis of the sample cannot be directly performed. Therefore, sample pretreatment, i.e., separation and enrichment of a sample is required to separate a component to be measured from other components in the sample as much as possible, and the concentration can meet the requirements of a measuring instrument.
Therefore, in order to overcome the defects of the prior art, a method for analyzing a piperidinol compound is needed.
Disclosure of Invention
In view of the above problems, an object of the present invention is to provide a method for analyzing a piperidinol compound.
In order to realize the purpose, the invention adopts the following technical scheme: an analytical method for a piperidinol compound, said analytical method selected from the group consisting of a hollow fiber liquid phase microextraction and a liquid chromatography coupled analytical method.
The analysis method according to the present invention, wherein the analysis method comprises the steps of:
cutting the hollow fiber into 3cm small sections, placing the small sections in chromatographic pure acetone for ultrasonic cleaning, and naturally airing;
placing the dried hollow fiber in ethyl acetate for ultrasonic rinsing to form a micro-liquid film;
taking out the hollow fiber, sleeving the hollow fiber on the needle point of the micro syringe, pushing out the ethyl acetate, and thermally sealing two ends of the hollow fiber;
putting the heat-sealed hollow fiber into a sample solution for extraction;
after extraction, one end of the hollow fiber is cut, the ethyl acetate solution is pumped back, and the ethyl acetate solution is injected into a high performance liquid chromatograph for analysis.
The analytical method according to the present invention, wherein the hollow fiber is selected from a polypropylene hollow fiber.
The analysis method of the present invention, wherein the hollow fiber has a wall thickness of 100 to 300 μm, an inner diameter of 400 to 800 μm, and a pore diameter of 0.1 to 0.3 μm.
Preferably, the hollow fiber has a wall thickness of 150 to 250 μm, an inner diameter of 500 to 700 μm, and a pore diameter of 0.15 to 0.25 μm.
The analytical method according to the present invention, wherein the hollow fiber has a porosity of 60 to 90%.
Preferably, the hollow fiber has a porosity of 70 to 80%.
The analytical method according to the present invention, wherein the chromatographic conditions are: an Agilent ZORBAXSB-Aq C18 column liquid chromatography column (250 mm. Times.4.6 mm,5 μm); mobile phase 70/30 MeOH/H by volume 2 O; the flow rate is 0.8mL/min; the detection wavelength is 260nm; the sample injection amount is 5 mu L; column temperature: at 30 ℃.
The analysis method provided by the invention is characterized in that the extraction temperature is 30-50 ℃, and the extraction time is 15-45min.
Preferably, the extraction temperature is 35-45 ℃, and the extraction time is 20-40min.
The analytical method according to the present invention, wherein the extraction is performed under stirring.
Advantageously, the stirring rate is between 300 and 500rpm; preferably 350-450rpm.
The analytical method according to the present invention, wherein the piperidinol compound is selected from the group consisting of (R) -1-benzyl-3-piperidinol, (S) -1-benzyl-3-piperidinol, and racemic 1-benzyl-3-piperidinol.
The invention has the following beneficial technical effects: compared with the conventional liquid chromatography method, the method can realize the enrichment of 1-benzyl-3-piperidinol, the enrichment multiple is as high as tens of times, and the detection limit is obviously reduced, so that the sensitivity of the analysis method is improved.
Detailed Description
The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how the compounds, compositions, articles, devices, and/or methods described and claimed herein are made and evaluated, and are intended to be purely exemplary and are not intended to limit the scope of what the inventors regard as their invention. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.) but some errors and deviations should be accounted for.
Unless otherwise indicated, parts are parts by weight, temperatures are in degrees celsius or at ambient temperature, and pressures are at or near atmospheric. There are many variations and combinations of reaction conditions (e.g., component concentrations, desired solvents, solvent mixtures, temperatures, pressures, and other reaction ranges) and conditions that can be used to optimize the purity and yield of the product obtained by the process. Only reasonable routine experimentation will be required to optimize such process conditions.
Example 1
The analysis method of the racemic 1-benzyl-3-piperidinol is selected from the analysis methods of hollow fiber liquid phase micro-extraction and liquid chromatography combination.
The hollow fiber is purchased from Membrana company of Germany, the wall thickness of the hollow fiber is 150-250 μm, the inner diameter is 500-700 μm, and the pore diameter is 0.15-0.25 μm; the porosity of the hollow fiber was 75%.
The analysis method comprises the following steps:
cutting the hollow fiber into 3cm small segments, placing in chromatographic pure acetone, ultrasonically cleaning for 5min, and naturally drying;
placing the dried hollow fiber in ethyl acetate for ultrasonic rinsing to ensure that the ethyl acetate uniformly enters the porous wall of the hollow fiber to form a micro-liquid film;
taking out the hollow fiber, sleeving the hollow fiber on the needle point of the micro syringe, pushing out the ethyl acetate, and thermally sealing two ends of the hollow fiber;
putting the heat-sealed hollow fiber into a sample solution for extraction; the extraction temperature is 40 ℃, and the extraction time is 30min. The extraction was carried out under stirring at a rate of 400rpm.
After extraction, one end of the hollow fiber is cut, the ethyl acetate solution is pumped back, and the ethyl acetate solution is injected into a high performance liquid chromatograph for analysis.
The chromatographic conditions are as follows: an Agilent ZORBAX SB-Aq C18 column liquid chromatography column (250 mm. Times.4.6 mm,5 μm); mobile phase 70/30 MeOH/H by volume 2 O; the flow rate is 0.8mL/min; the detection wavelength is 260nm; the sample size is 5 mu L; column temperature: at 30 ℃.
Accurately weighing 0.0500g of 1-benzyl-3-piperidinol, dissolving with methanol, and metering to a 50mL volumetric flask to obtain 1-benzyl-3-piperidinol standard stock solution with the concentration of 1.0 g/L. Standard solutions of different concentrations were prepared from this stock solution diluted with secondary water.
The standard solutions with different concentrations are extracted according to the method, and are measured and plotted under the chromatographic conditions to obtain a working curve equation of H =39.451C +6.816 (wherein H is peak height and C is concentration). The 1-benzyl-3-piperidinol has good linear relation in the range of 0.01-5.0mg/L, and the correlation coefficient is 0.9998.
The extraction was carried out according to the above method using a standard solution of 0.01mg/L concentration and was repeated 11 times under the above chromatographic conditions, with an RSD of 2.9%. The signal-to-noise ratio S/N is taken as 3, and the detection limit is calculated to be 0.87 mu g/L.
Furthermore, the standard solutions with concentrations of 0.05mg/L, 0.1mg/L, and 0.5mg/L were extracted according to the above-mentioned methods, and the respective enrichment factors of the three were calculated as 86.2, 64.7, and 39.1 from the chromatograms before and after the respective extractions.
Comparative example 1
Accurately weighing 0.0500g of 1-benzyl-3-piperidinol, dissolving with methanol, and metering to a 50mL volumetric flask to obtain 1-benzyl-3-piperidinol standard stock solution with the concentration of 1.0 g/L. Standard solutions of different concentrations were prepared from this stock solution diluted with secondary water.
The standard solutions with different concentrations are directly measured and plotted under the chromatographic conditions to obtain a working curve equation of H =1.362C +3.587 (wherein H is peak height, and C is concentration). The 1-benzyl-3-piperidinol has good linear relation in the range of 0.5-80mg/L, and the correlation coefficient is 0.9997.
The standard solution with a concentration of 0.5mg/L was extracted as described above and determined under the above chromatographic conditions to be repeated 11 times with an RSD of 3.4%. The signal-to-noise ratio S/N is taken as 3, and the detection limit is calculated to be 51 mu g/L.
It should be understood that the detailed description of the invention is merely illustrative of the spirit and principles of the invention and is not intended to limit the scope of the invention. Furthermore, it should be understood that various changes, substitutions, deletions, modifications or adjustments may be made by those skilled in the art after reading the disclosure of the present invention, and such equivalents are also within the scope of the invention as defined in the appended claims.
Claims (4)
1. An analytical method for a piperidinol compound, the analytical method selected from the group consisting of a hollow fiber liquid phase microextraction and a liquid chromatography combined analytical method;
the analysis method comprises the following steps:
cutting the hollow fiber into 3cm small sections, placing the small sections in chromatographic pure acetone for ultrasonic cleaning, and naturally airing;
placing the dried hollow fiber in ethyl acetate for ultrasonic rinsing to form a micro-liquid film;
taking out the hollow fiber, sleeving the hollow fiber on the needle point of the micro syringe, pushing out the ethyl acetate, and thermally sealing two ends of the hollow fiber;
putting the heat-sealed hollow fiber into a sample solution for extraction;
after extraction, cutting one end of the hollow fiber, withdrawing the ethyl acetate solution, and injecting into a high performance liquid chromatograph for analysis;
the hollow fibers are selected from polypropylene hollow fibers; the wall thickness of the hollow fiber is 100-300 μm, the inner diameter is 400-800 μm, and the aperture is 0.1-0.3 μm; the porosity of the hollow fiber is 60-90%;
the chromatographic conditions are as follows: an Agilent ZORBAX SB-Aq C18 column liquid chromatography column; mobile phase 70/30 MeOH/H by volume 2 O; the flow rate is 0.8mL/min; the detection wavelength is 260nm; the sample injection amount is 5 mu L; column temperature: 30 ℃;
the piperidinol compound is selected from (R) -1-benzyl-3-piperidinol, (S) -1-benzyl-3-piperidinol or racemic 1-benzyl-3-piperidinol.
2. The analytical method according to claim 1, wherein the extraction temperature is 30 to 50 ℃ and the extraction time is 15 to 45min.
3. The analytical method of claim 1, wherein the extraction is performed under agitation conditions.
4. An assay according to claim 3, wherein the agitation rate is from 300 to 500rpm.
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| CN202110859211.0A CN113640408B (en) | 2021-07-28 | 2021-07-28 | Method for analyzing piperidinol compound |
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| CN202110859211.0A CN113640408B (en) | 2021-07-28 | 2021-07-28 | Method for analyzing piperidinol compound |
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| CN113640408B true CN113640408B (en) | 2023-03-07 |
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Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2445316A1 (en) * | 2001-04-26 | 2002-11-07 | Varian, Inc. | Hollow fiber membrane sample preparation devices |
| US20060013981A1 (en) * | 2004-07-19 | 2006-01-19 | University Of South Florida | Polytetrahydrofuran-Based Coating for Capillary Microextraction |
| US20090263346A1 (en) * | 2006-12-05 | 2009-10-22 | David Taft | Systems and methods for delivery of drugs |
| CN111848495B (en) * | 2020-06-02 | 2022-06-21 | 山东华素制药有限公司 | Synthesis method of 1-benzyl-3-piperidinol |
| CN112138428B (en) * | 2020-09-18 | 2021-12-31 | 华中科技大学 | Flat membrane type liquid phase micro-extraction method and application thereof in drug extraction |
| CN112162046A (en) * | 2020-09-25 | 2021-01-01 | 宁波大红鹰药业股份有限公司 | Quantitative analysis method for extremely-low-concentration haloperidol in blood plasma |
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