CN117866019A - Synthesis method of 1,3-N, N-diethyl-galectin - Google Patents

Synthesis method of 1,3-N, N-diethyl-galectin Download PDF

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CN117866019A
CN117866019A CN202311801989.1A CN202311801989A CN117866019A CN 117866019 A CN117866019 A CN 117866019A CN 202311801989 A CN202311801989 A CN 202311801989A CN 117866019 A CN117866019 A CN 117866019A
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王晓霞
毛菊红
李培鹏
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Wuxi Jiyu Shanhe Pharmaceutical Co ltd
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Abstract

The invention relates to a synthesis method of 1,3-N, N-diethyl-Galosamine, which comprises the following steps: weighing scaleTaking etimicin sulfate, adding the etimicin sulfate into a reaction bottle, and adding H 2 O is dissolved, ferrocene is added, hydrogen peroxide is dripped, heating reflux is carried out, after reaction, methanol is added for quenching reaction, suction filtration is carried out to remove insoluble ferrocene, after the filtrate is completely dried in a spinning way, a proper amount of methanol is added, the pH value is regulated to 2-3 by dilute hydrochloric acid to be dissolved, the solution is reddish brown, suction filtration is carried out to remove sediment, brown oily matter is obtained after the filtrate is dried in a spinning way, silica gel column chromatography is adopted to purify 1-N-ethyl galanthamine, 1-N-ethyl galanthamine is weighed, the mixture is added into a reaction bottle, methanol is added for dissolution, acetic acid is dripped under the low temperature condition, acetaldehyde solution is dripped into the mixture, naBH is added 4 And (3) reacting at normal temperature, after the reaction is finished, dropwise adding a hydrochloric acid solution to quench the reaction, spinning the reaction solution, adding a proper amount of methanol to dissolve the reaction solution, filtering to remove insoluble salt, spinning the filtrate to obtain a light yellow solid, and purifying the 1,3-N, N-diethyl-galanthamine by adopting silica gel column chromatography.

Description

Synthesis method of 1,3-N, N-diethyl-galectin
Technical Field
The invention relates to a synthesis method of a drug intermediate, in particular to a synthesis method of 1,3-N, N-diethyl-galectin, and specifically relates to a method for synthesizing 1,3-N, N-diethyl-galectin by etimicin.
Background
Etimicin (ETM, aidamycin, synergy, 89-07) is a new medicine with independent intellectual property rights which is researched and developed by scientific personnel in China, is ethylation semisynthetic aminoglycoside antibiotics of gentamicin C1a, and has good curative effects on respiratory tract infection, urinary system infection, skin soft tissue infection and the like. The medicine has low adverse reaction, good cross resistance and ototoxicity far less than other similar products, and is a safe and effective new anti-infective medicine. The stable and controllable medicine quality is the premise and the foundation for ensuring the safety and effectiveness of medicines, and the research on medicine related substances is the important content of medicine quality control.
The early stage research uses chromatographic and spectrum method to separate and identify the related substances of etimicin as raw material, and separates and identifies 11 related substances of aminoglycoside, wherein the compound 1,3-N, N-diethyl-galectin is new compound.
The chemical structure is as follows:
1,3-N, N-diethyl-Galosamine 1 H, 13 C NMR data are shown in Tab.1. Nuclear magnetic resonance spectrum analysis
Tab 1.1,3-N, N-diethyl-gulose 1 H-NMR、 13 C NMRData
At present, no report on a related synthesis process of 1,3-N, N-diethyl-Galosamine exists, the synthesis process of the 1,3-N, N-diethyl-Galosamine is adopted as the only synthesis process of the 1,3-N, N-diethyl-Galosamine, the synthesis route is simple, the operation is convenient, the use time is short, the cost is low, the environmental pollution is small, and the 1,3-N, N-diethyl-Galosamine prepared by the method has the characteristics of high purity, high yield and the like, and has great significance for improving the quality of medicines and improving the safety of clinical medication.
No standard products of 1,3-N, N-diethyl-Galosamine are sold at home and abroad, and no relevant literature report exists. The content of 1,3-N, N-diethyl-galectin in etimicin bulk drugs is low, and sufficient 1,3-N, N-diethyl-galectin is difficult to obtain by a separation method, so that a chemical synthesis method is adopted to carry out batch synthesis of 1,3-N, N-diethyl-galectin by a simple and efficient method, so that the method is used for pharmaceutical analysis of etimicin.
Therefore, the invention provides an impurity control method for etimicin sulfate bulk drug and preparation thereof, in particular to a content determination method for 1,3-N, N-diethyl-galectin, and the invention further provides a preparation method for 1,3-N, N-diethyl-galectin serving as an impurity reference substance. The invention has great significance for improving the quality of medicines and improving the safety of clinical medication.
Disclosure of Invention
The invention aims to provide a 1,3-N, N-diethyl-galectin amine compound, a preparation method thereof and application of the 1,3-N, N-diethyl-galectin amine as an impurity reference substance in the process of detecting etimicin.
1,3-N, N-diethyl-galectin amine has the following chemical structure:
the preparation method of the 1,3-N, N-diethyl-Galosamine comprises the following synthetic route:
the preparation method provided by the invention comprises the following steps:
1) Weighing etimicin sulfate, adding into a reaction bottle, and adding H 2 O is dissolved, ferrocene is added, hydrogen peroxide is added dropwise, heating reflux is carried out, methanol is added for quenching reaction after reaction, and insoluble ferrocene is removed by suction filtration.
2) After the filtrate is completely dried, adding a proper amount of methanol and adjusting the pH to 2-3 with dilute hydrochloric acid for dissolution, removing the precipitate by suction filtration, and obtaining brown oily matter after the filtrate is dried by spinning.
3) Purifying 1-N-ethyl-galanthamine by silica gel column chromatography.
4) Weighing 1-N-ethyl-galanthamine, adding into a reaction bottle, adding methanol for dissolution, dropwise adding acetic acid at low temperature, dropwise adding acetaldehyde solution, and adding NaBH 4 And (3) reacting at normal temperature.
5) After the reaction is finished, hydrochloric acid solution is added dropwise to quench the reaction. Spin-drying the reaction solution, adding a proper amount of methanol for dissolution, filtering to remove insoluble salts, and spin-drying the filtrate to obtain a pale yellow solid.
6) Purifying 1,3-N, N-diethyl-galectin by silica gel column chromatography.
Wherein, the mole ratio of etimicin sulfate to ferrocene in the step (1) is 4:1-8:1.
Preferably, the molar ratio of etimicin sulfate to ferrocene in step (1) is 6:1.
Wherein the mole ratio of etimicin sulfate to hydrogen peroxide in the step (1) is 4:1-8:1.
Preferably, the molar ratio of etimicin sulfate to hydrogen peroxide in step (1) is 6:1.
Wherein, the temperature in the step (1) is between minus 25 and 60 ℃ and the reflux is carried out for 2 to 9 hours.
Preferably, the temperature in step (1) is refluxed at 40℃for 5 hours.
Wherein the mole ratio of etimicin sulfate to methanol in the step (1) is 1:50-1:100.
Preferably, the molar ratio of etimicin sulfate to methanol in step (1) is 1:71.
Wherein the pH in the step (2) ranges from 1 to 6.
Preferably, the pH in step (2) is in the range of 2-3.
Wherein the eluent ratio of dichloromethane-methanol-ammonia water (25%) in the step (3) is 1:1:1-4:1:1.
Preferably, the eluent ratio in the step (3) is 2.5:1:1 in methylene chloride-methanol-ammonia (25%). Wherein the molar ratio of the 1-N-ethyl-Galosamine to the acetaldehyde in the step (4) is 1:1-1:4.
Preferably, the molar ratio of 1-N-ethyl-galectin amine to acetaldehyde in step (4) is 1:3.
Wherein the molar ratio of the 1-N-ethyl-Galosamine to the acetic acid in the step (4) is 1:4-1:7.
Preferably, the molar ratio of 1-N-ethyl-Galosamine to acetic acid in step (4) is 1:6.
Wherein, the heating temperature in the step (4) is 0-25 ℃, and the reflux is carried out for 1-5 h.
Preferably, the heating temperature in the step (4) is 5 ℃, and the reflux is carried out for 1h.
Wherein the molar ratio of the 1-N-ethyl-Galosamine to the sodium borohydride in the step (4) is 1:1-1:4.
Preferably, the molar ratio of 1-N-ethyl-galectin amine to sodium borohydride in step (4) is 1:3.
Wherein, the heating temperature in the step (4) is 0-40 ℃, and the reflux is carried out for 1-5 h.
Preferably, the heating temperature in the step (4) is 25 ℃, and the reflux is carried out for 1h.
Wherein the eluent ratio in the step (6) is 3:1:1-6:1:1 by weight of chloroform-methanol-ammonia water (25%).
Preferably, the eluent ratio in the step (6) is 5:1:1 chloroform-methanol-ammonia (25%).
Further preferably, the preparation method of the present invention comprises the steps of:
a. 2g of etimicin sulfate is weighed and added into a 100mL reaction bottle, and 39.4mL of H is added 2 O is dissolved, 0.108g of ferrocene is added, 0.6mL of 30 percent hydrogen peroxide is added dropwise, heating reflux is carried out at 40 ℃, after reaction is carried out for 5 hours,
the reaction was quenched by adding 10mL of methanol and the insoluble ferrocene was removed by suction filtration.
b. After the filtrate is completely dried, a proper amount of methanol is added and the pH is adjusted to 2-3 by 1M dilute hydrochloric acid for dissolution, the solution is reddish brown, the precipitate is removed by suction filtration, and the brown oily matter is obtained after the filtrate is dried by spinning.
c. Purifying 1-N-ethyl-galanthamine by silica gel column chromatography. Mobile phase system: 1-N-ethyl-Galosamine was separated and purified in a ratio of 2.5:1:1 with methylene chloride-methanol-ammonia (25%) and the lower layer was removed.
d. 30mg of 1-N-ethyl-Galosamine is weighed, added into a 50mL reaction bottle, 10mL of methanol is added for dissolution, 30 mu L of acetic acid is added dropwise at 5 ℃, 51 mu L of acetaldehyde solution is added dropwise, and the reaction is carried out for 1h. 9.6mg NaBH was added 4 The reaction was carried out at room temperature for 1h.
e. After the completion of the reaction, the reaction was quenched by dropwise addition of 0.5mL of a 1M hydrochloric acid solution. Spin-drying the reaction solution, adding a proper amount of methanol for dissolution, filtering to remove insoluble salts, and spin-drying the filtrate to obtain a pale yellow solid.
f. Purifying 1,3-N, N-diethyl-galectin by silica gel column chromatography. Mobile phase system: chloroform-methanol-ammonia (25%), 5:1:1, the lower layer was removed.
The invention further provides a detection method of 1,3-N, N-diethyl-Galosamine, which is characterized by comprising the following steps:
12.5mg of 1, 3-N-ethyl-Galosamine is weighed, placed in a 5ml volumetric flask, diluted to a scale with water, and prepared into a test solution.
And (3) injecting the mixture into a liquid chromatograph to obtain a chromatogram, and calculating the content of the 1, 3-N-ethyl-galanthamine in the sample solution according to the chromatogram by an area normalization method.
Chromatographic conditions:
chromatographic column: gemini NX C18 (4.6 mm. Times.150 mm,5 μm); mobile phase: phase A: water-ammonia-glacial acetic acid (96:3.6:0.4), phase B: methanol, gradient elution (see Tab 1 for procedure); flow rate: 1ml/min; column temperature: 30 ℃; sample injection amount: 10 μl; ELSD parameters: drift tube temperature: 106 ℃; carrier gas flow rate: 2.9L/min; gain value: 1.
tab 1 mobile phase gradient
The invention further provides a detection method of etimicin and the impurity 1,3-N, N-diethyl-galectin thereof, which is characterized by comprising the following steps:
etimicin 43mg is weighed, placed in a 100ml volumetric flask, diluted with water to a scale, and prepared into a test solution.
1ml of the sample solution is precisely measured, placed in a 100ml volumetric flask, diluted to a scale with water, and prepared into a reference sample solution.
Standard 1,3-N, N-diethyl-galectin 0.5308mg was weighed and placed in a 25ml volumetric flask, diluted to a scale with water, and a pair of sample solutions were prepared.
Injecting the mixture into a Thermo ICS5000+ ion chromatograph to obtain a chromatogram, and calculating the content of 1, 3-N-ethyl-Galosamine in the sample solution according to the chromatogram.
Chromatographic conditions:
tab 2.LC-PAD detection method
At present, no report on a related synthesis process of 1,3-N, N-diethyl-Galosamine exists, the synthesis process of the 1,3-N, N-diethyl-Galosamine is adopted as the only synthesis process of the 1,3-N, N-diethyl-Galosamine, the synthesis route is simple, the operation is convenient, the use time is short, the cost is low, the environmental pollution is small, and the 1,3-N, N-diethyl-Galosamine prepared by the method has the characteristics of high purity, high yield and the like, and has great significance for improving the quality of medicines and improving the safety of clinical medication.
The invention discloses an enzyme-linked immunosorbent assay method of etimicin. The detection method comprises the steps of coating the etimicin antibody on a solid phase carrier, adding a standard sample or a sample to be detected, adding an enzyme-labeled etimicin antibody, adding a substrate solution for color development after reaction, measuring the percentage absorbance, calculating the concentration of etimicin in the sample to be detected according to the standard curve of etimicin and the percentage absorbance value of the sample to be detected, and the like.
Drawings
FIG. 1.1H-NMR spectrum (D2O 400 MHz)
FIG. 2.13C-NMR spectrum (D2O 100 MHz)
FIG. 3 TLC chromatogram of degraded reaction solution
1. 2: after the reaction liquid is treated; 3. 4: 1-N-ethyl-galanthamine control; 5. 6: degradation reaction liquid
FIG. 4.1-HPLC-ELSD chromatogram of N-ethyl-gulosamine reaction solution
FIG. 5.1,3-TLC chromatogram of N, N-diethyl-Galosamine reaction solution
1. 2, 4, 5:1,3-N, N-diethyl-galectin amine reaction solution; 3:1,3-N, N-diethyl-Galosamine control
B:1,3-N, N-diethyl-galanthamine; A. c: byproducts; d: 1-N-ethyl-Galosamine
FIG. 6.1,3-N, N-diethyl-Galosamine HPLC-ELSD chromatogram
FIG. 7 ion chromatography of 1,3-N, N-diethyl-Galosamine
FIG. 8 ion chromatogram of etimicin product
Detailed description of the preferred embodiments
The invention is further illustrated, but not limited, by the following specific examples
EXAMPLE 1 Synthesis of 1-N-ethyl-Galosamine
Fenton reaction degradation etimicin
2g of etimicin sulfate is weighed and added into a 100mL reaction bottle, and 39.4mL of H is added 2 O is dissolved, 0.108g of ferrocene is added, 0.6mL of 30% hydrogen peroxide is added dropwise, the mixture is heated and refluxed at 40 ℃, after 5 hours of reaction, 10mL of methanol is added for quenching reaction, and insoluble ferrocene is removed by suction filtration. And 2g of each time of feeding, combining reaction solutions of four reactions, completely spinning the filtrate, adding a proper amount of methanol, adjusting the pH to 2-3 with 1M dilute hydrochloric acid for dissolution, removing precipitates by suction filtration, and obtaining about 2.5g of brown oily matter after spinning the filtrate.
TLC detection (developing solvent: chloroform-methanol-ammonia water (25%), 1:1:1,lower layer,I 2 Color development), and the reaction solution and the oil obtained after the treatment (fig. 3.) were examined, and it was found that other impurities than etimicin starting material were significantly reduced, while the loss of the product 1-N-ethyl-gulosamine was small, which was advantageous for the subsequent separation and purification by column chromatography. Mobile phase system: dichloromethane-methanol-ammonia (25%), 2.5:1:1, the lower layer was taken and 1 silica gel (200-300 mesh) wet packed. The pure 1-N-ethyl-galanthamine can be obtained as a reddish brown oily substance. The purity of the isolated and purified 1-N-ethyl-Galosamine was 93.82% (FIG. 4.).
EXAMPLE 2 Synthesis of 1,3-N, N-diethyl-Galosamine
30mg of 1-N-ethyl-Galosamine is weighed, added into a 50mL reaction bottle, 10mL of methanol is added for dissolution, 30 mu L of acetic acid is added dropwise at 5 ℃, 51 mu L of acetaldehyde solution is added dropwise, and the reaction is carried out for 1h. 9.6mg NaBH was added 4 The reaction was carried out at room temperature for 1h. After the completion of the reaction, the reaction was quenched by dropwise addition of 0.5mL of a 1M hydrochloric acid solution. Spin-drying the reaction solution, adding a proper amount of methanol for dissolution, filtering to remove insoluble salts, and spin-drying the filtrate to obtain a pale yellow solid.
TLC detection of reaction solutions (developing agent: chloroform-methanol-ammonia water (25%), 1:1:1,lower layer,I 2 Color development) (fig. 5.) produced mainly 2 by-products with 1-N-ethyl-galanthamine residues.
Purifying 1,3-N, N-diethyl-galectin by silica gel column chromatography. Mobile phase system: chloroform-methanol-ammonia (25%), 5:1:1, the lower layer was taken; silica gel (200-300 mesh) is packed in a column by a wet method, and the beige solid 1,3-N, N-diethyl-galectin amine pure product can be obtained by separation. The purity of 1,3-N, N-diethyl-galectin (19.27 min) obtained by separation and purification was 99.38% (FIG. 6.). Meets the related technical requirements of the research on chemical drug impurity reference substances.
(1) Firstly, synthesizing 1-N-ethyl-Galosamine by etimicin;
(2) Synthesizing 1,3-N, N-diethyl-galanthamine by 1-N-ethyl galanthamine;
according to the research of the invention, the degradation impurity of etimicin sulfate is generated in the storage process of etimicin sulfate, but the content is low and is difficult to find, the invention synthesizes 1,3-N, N-diethyl-galectin sulfate and researches a content measuring method thereof in order to solve the quality assurance in the storage of etimicin sulfate raw materials. The method adopts the easy-to-obtain etimicin sulfate as the starting material to synthesize the target, and has the characteristics of lower cost, higher conversion rate and high separation purity.

Claims (9)

1.1,3-N, N-diethyl-Galosamine has the following chemical structure:
2. a process for the preparation of 1,3-N, N-diethyl-galectin as defined in claim 1, which comprises the following synthetic routes:
3. the method of manufacturing as claimed in claim 2, comprising the steps of:
(1) Weighing etimicin sulfate, adding into a reaction bottle, and adding H 2 O is dissolved, ferrocene is added, hydrogen peroxide is added dropwise, heating reflux is carried out, methanol is added for quenching reaction after reaction, and insoluble ferrocene is removed by suction filtration;
(2) Adding a proper amount of methanol after the filtrate is completely dried by spinning, regulating the pH to 2-3 by using dilute hydrochloric acid, dissolving, removing precipitate by suction filtration when the solution is reddish brown, and obtaining brown oily matter after the filtrate is dried by spinning;
(3) Purifying 1-N-ethyl-galanthamine by silica gel column chromatography;
(4) Weighing 1-N-ethyl-galanthamine, adding into a reaction bottle, adding methanol for dissolution, dropwise adding acetic acid at low temperature, dropwise adding acetaldehyde solution, and adding NaBH 4 Reacting at normal temperature;
(5) After the reaction is finished, hydrochloric acid solution is added dropwise to quench the reaction. Spin-drying the reaction solution, adding a proper amount of methanol for dissolution,
filtering to remove insoluble salt, and spin-drying the filtrate to obtain pale yellow solid;
(6) Purifying 1,3-N, N-diethyl-galectin by silica gel column chromatography.
4. The method according to claim 3, wherein,
wherein, the mole ratio of etimicin sulfate to ferrocene in the step (1) is 4:1-8:1;
wherein, the mole ratio of etimicin sulfate to hydrogen peroxide in the step (1) is 4:1-8:1;
wherein, the temperature in the step (1) is between 25 ℃ below zero and 60 ℃ for 2 to 9 hours;
wherein, the mole ratio of etimicin sulfate to methanol in the step (1) is 1:50-1:100;
wherein the pH in the step (2) ranges from 1 to 6;
wherein the eluent ratio of dichloromethane-methanol-ammonia water (25%) in the step (3) is 1:1:1-4:1:1;
wherein, the mol ratio of the 1-N-ethyl-Galosamine to the acetaldehyde in the step (4) is 1:1-1:4;
wherein, the mol ratio of the 1-N-ethyl-Galosamine to the acetic acid in the step (4) is 1:4-1:7;
wherein, the heating temperature in the step (4) is 0-25 ℃, and the reflux is carried out for 1-5 h;
wherein the molar ratio of the 1-N-ethyl-galanthamine to the sodium borohydride in the step (4) is 1:1-1:4;
wherein, the heating temperature in the step (4) is 0-40 ℃, and the reflux is carried out for 1-5 h;
wherein the eluent ratio in the step (6) is 3:1:1-6:1:1 by weight of chloroform-methanol-ammonia water (25%).
5. The method according to claim 4, wherein,
wherein, the mole ratio of etimicin sulfate to ferrocene in the step (1) is 6:1;
wherein, the mole ratio of etimicin sulfate to hydrogen peroxide in the step (1) is 6:1;
wherein, the temperature in the step (1) is refluxed for 5 hours at 40 ℃;
wherein, the mole ratio of etimicin sulfate to methanol in the step (1) is 1:71;
wherein the pH range in the step (2) is 2-3;
wherein the eluent ratio of dichloromethane-methanol-ammonia water (25%) in the step (3) is 2.5:1:1;
wherein, the mol ratio of the 1-N-ethyl-galanthamine to the acetaldehyde in the step (4) is 1:3;
wherein, the molar ratio of the 1-N-ethyl-galanthamine to the acetic acid in the step (4) is 1:6;
wherein, the heating temperature in the step (4) is 5 ℃, and the reflux is carried out for 1h;
wherein, the mol ratio of the 1-N-ethyl-galanthamine to the sodium borohydride in the step (4) is 1:3;
wherein, the heating temperature in the step (4) is 25 ℃, and the reflux is carried out for 1h; wherein the eluent ratio in the step (6) is 5:1:1 by weight of chloroform-methanol-ammonia water (25%).
6. A method of preparation as claimed in claim 3, characterized by the steps of:
a. 2g of etimicin sulfate is weighed and added into a 100mL reaction bottle, and 39.4mL of H is added 2 O is dissolved, 0.108g of ferrocene is added, 0.6mL of 30% hydrogen peroxide is added dropwise, heating reflux is carried out at 40 ℃, after reaction is carried out for 5 hours, 10mL of methanol is added for quenching reaction, and insoluble ferrocene is removed by suction filtration;
b. adding a proper amount of methanol after the filtrate is completely dried by spinning, adjusting the pH to 2-3 by using 1M dilute hydrochloric acid, dissolving, removing precipitate by suction filtration to obtain brown oily matter after the filtrate is dried by spinning;
c. purifying 1-N-ethyl-galanthamine by silica gel column chromatography. Mobile phase system: separating and purifying 1-N-ethyl-galanthamine by using methylene dichloride-methanol-ammonia water (25%) in a ratio of 2.5:1:1, and taking a lower layer;
d. 30mg of 1-N-ethyl-Galosamine is weighed, added into a 50mL reaction bottle, 10mL of methanol is added for dissolution, 30 mu L of acetic acid is added dropwise at 5 ℃, 51 mu L of acetaldehyde solution is added dropwise, and the reaction is carried out for 1h. 9.6mg NaBH was added 4 Reacting for 1h at room temperature;
e. after the completion of the reaction, the reaction was quenched by dropwise addition of 0.5mL of a 1M hydrochloric acid solution. Spin-drying the reaction solution, adding a proper amount of methanol for dissolution, filtering to remove insoluble salts, and spin-drying the filtrate to obtain a pale yellow solid;
f. purifying 1,3-N, N-diethyl-galectin by silica gel column chromatography; mobile phase system: chloroform-methanol-ammonia (25%), 5:1:1, the lower layer was removed.
7.1,3-N, N-diethyl-Galamin is used as impurity reference substance in etimicin detection process.
8. The detection method of the 1,3-N, N-diethyl-galanthamine is characterized by comprising the following steps:
weighing 12.5mg of 1,3-N, N-diethyl-galectin, placing in a 5ml volumetric flask, diluting with water to scale, and preparing into a sample solution;
injecting into a liquid chromatograph to obtain a chromatogram, and calculating the content of 1,3-N, N-diethyl-galanthamine in the sample solution according to the chromatogram by an area normalization method;
chromatographic column: gemini NX C18; mobile phase: phase A: water-ammonia-glacial acetic acid (96:3.6:0.4), phase B: methanol; flow rate: 1ml/min; column temperature: 30 ℃; sample injection amount: 10 μl; ELSD parameters: drift tube temperature: 106 ℃; carrier gas flow rate: 2.9L/min; gain value: 1.
9. a method for detecting etimicin and impurity 1,3-N, N-diethyl-galectin thereof is characterized by comprising the following steps:
weighing etimicin 43mg, placing in a 100ml volumetric flask, diluting with water to scale, and preparing into test solution;
precisely measuring 1ml of sample solution, placing in a 100ml volumetric flask, diluting with water to scale, and preparing into a sample solution;
weighing 0.5308mg of standard 1,3-N, N-diethyl-gulose, placing in a 25ml volumetric flask, diluting with water to scale, and preparing a reference solution;
injecting the mixture into a Thermo ICS5000+ ion chromatograph to obtain a chromatogram, and calculating the content of 1,3-N, N-diethyl-gulose in the sample solution according to the chromatogram;
LC-PAD detection method:
chromatographic column: welch LP-C18: mobile phase: 0.2mol/L trifluoroacetic acid (50% sodium hydroxide solution containing 0.05% pentafluoropropionic acid, 1.5g/L anhydrous sodium sulfate, 0.8% (V/V), adjusting the pH to 3.5 with 50% sodium hydroxide solution) -acetonitrile (96:4); flow rate: 1ml/min; column temperature: 35 ℃; sample injection amount: 25 μl.
CN202311801989.1A 2023-12-26 2023-12-26 Synthesis method of 1,3-N, N-diethyl-galectin Pending CN117866019A (en)

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