Analysis method of benzothiazole compound isomer

Abstract

The invention discloses a benzothiazole compound isomer analysis method, which comprises: (1) taking a sample to be detected, treating with an organic solvent, and preparing into a test sample solution, the sample to be detected containing pamoate of a compound I (S)-2-amino-4, 5, 6, 7-tetrahydro-6-propylamine-benzothiazole; and (2) carrying out separation and determination by adopting normal phase-high performance liquid chromatography, wherein a chemical bonding type chiral chromatographic column is selected as a chromatographic column. The analysis method disclosed by the invention is simple and convenient to operate, short in analysis period and strong in specificity, and isomers in the compound I pamoate bulk drug and the preparation can be effectively controlled.

Description

Technical Field

[0001] The invention belongs to the field of drug analysis, and particularly relates to a method for analyzing isomers in benzothiazole compound raw materials or preparations by using normal phase-high performance liquid chromatography. Background Art

[0002] (S)-2-Amino-4,5,6,7-tetrahydro-6-propylamine-benzothiazole (hereinafter referred to as "Compound I") is a non-ergot dopamine receptor agonist used to treat patients with primary Parkinson's disease. Currently, the products available on the market in China and abroad are mainly hydrochloride immediate-release tablets and hydrochloride sustained-release tablets.

[0003] Oral preparations require frequent dosing to maintain therapeutic effects. Due to the high incidence of dysphagia in Parkinson's patients, oral administration can easily cause choking and coughing, increasing the risk of aspiration pneumonia. Long-acting sustained-release preparations, on the other hand, can prolong the duration of drug action, reduce the frequency of medication use, improve patient compliance, and reduce fluctuations in blood drug concentrations, thereby improving medication safety. These preparations are particularly suitable for psychiatric conditions, and therefore clinical development of long-acting sustained-release preparations is advocated. The pamoate salt of Compound I exhibits favorable properties compared to the hydrochloride salt and is currently being explored for application in long-acting sustained-release preparations.

[0004] Compound I contains a chiral center in its molecular structure, with enantiomers existing as (R)-2-amino-4,5,6,7-tetrahydro-6-propylamine-benzothiazole (hereinafter referred to as "Compound II"). Isomeric impurities may have completely different biological activities from the main component, making them a key factor in controlling impurities in chiral drugs. Prior art reports describe isomer analysis methods for Compound I hydrochloride. However, when used to detect isomers of Compound I pamoate, both in the bulk drug and in the formulation, these methods suffer from strong interference, poor sensitivity, and poor chromatographic column compatibility. Currently, no isomer analysis methods for Compound I pamoate have been reported. Therefore, it is of great significance to establish an isomer analysis method with good specificity, high sensitivity, and strong compatibility for Compound I pamoate. Summary of the Invention

[0005] The main purpose of the present invention is to provide a method for analyzing isomers in (S)-2-amino-4,5,6,7-tetrahydro-6-propylamine-benzothiazole pamoate, which is used to solve the problem of detecting isomers in the raw materials and preparations of (S)-2-amino-4,5,6,7-tetrahydro-6-propylamine-benzothiazole pamoate, thereby promoting the research on its quality control.

[0006] To achieve the above object, the technical solution of the present invention is as follows:

[0007] A method for analyzing isomers of benzothiazole compounds, comprising the following steps: (1) taking a sample to be tested, treating it with an organic solvent, and preparing a test solution, wherein the sample to be tested contains the pamoate salt of compound I(S)-2-amino-4,5,6,7-tetrahydro-6-propylamine-benzothiazole; and (2) performing separation and determination by normal phase-high performance liquid chromatography, wherein the chromatographic column is a chemically bonded chiral chromatographic column.

[0008] In some embodiments of the present invention, the chromatographic column is a polysaccharide derivative bonded chiral chromatographic column.

[0009] In some embodiments of the present invention, the chromatography column model is selected from DAICEL CHIRALPAK IA, DAICEL CHIRALPAK IB, DAICEL CHIRALPAK IC, DAICEL CHIRALPAK ID, DAICEL CHIRALPAK IE, DAICEL CHIRALPAK IF, DAICEL CHIRALPAK IG, DAICEL CHIRALPAK IH, DAICEL CHIRALPAK KIJ, DAICEL CHIRALPAK IK, DAICEL CHIRALPAK IM.

[0010] In some embodiments of the present invention, the chromatographic column model is selected from DAICEL CHIRALPAK IA, DAICEL CHIRALPAK IB, DAICEL CHIRALPAK IC, DAICEL CHIRALPAK ID, DAICEL CHIRALPAK IE, DAICEL CHIRALPAK IF, DAICEL CHIRALPAK IG, DAICEL CHIRALPAK IH, DAICEL CHIRALPAK KIJ, DAICEL CHIRALPAK IK, DAICEL CHIRALPAK IM, and the inner diameter of the chromatographic column is selected from 2.1 mm to 10 mm, the length is selected from 10 mm to 250 mm, and the particle size is selected from 1.6 μm to 10 μm.

[0011] In some embodiments of the present invention, the chromatography column model is selected from DAICEL CHIRALPAK IA (4.6×250 mm, 5 μm), DAICEL CHIRALPAK IB (4.6×250 mm, 5 μm), and DAICEL CHIRALPAK IC (4.6×250 mm, 5 μm).

[0012] In some embodiments of the present invention, the treatment with an organic solvent includes dissolution treatment, vortex treatment, ultrasonic treatment, or shaking treatment using an organic solvent.

[0013] In some embodiments of the present invention, the sample to be tested is the bulk drug of compound I pamoate.

[0014] In some embodiments of the present invention, the analysis method includes taking the bulk drug of compound I pamoate, dissolving it with an organic solvent, and preparing a test solution.

[0015] In some embodiments of the present invention, the organic solvent is selected from alcohol solvents.

[0016] In some embodiments of the present invention, the alcohol solvents are selected from one or more of methanol, ethanol, isopropanol or its isomers, n-butanol or its isomers.

[0017] In some embodiments of the present invention, the alcohol solvent is ethanol.

[0018] In some embodiments of the present invention, the sample to be tested is a preparation of compound I pamoate. Preferably, the preparation is a long-acting sustained-release preparation. More preferably, the preparation is a long-acting sustained-release microsphere preparation.

[0019] In some embodiments of the present invention, the analysis method includes taking the long-acting sustained-release preparation of compound I pamoate, subjecting it to vortex treatment with an organic solvent, and preparing a test solution.

[0020] In some embodiments of the present invention, the organic solvent is selected from aprotic polar solvents.

[0021] In some embodiments of the present invention, the aprotic polar solvents are selected from one or more of nitrile solvents, halogenated hydrocarbon solvents, furan solvents, ketone solvents, and amide solvents.

[0022] In some embodiments of the present invention, the aprotic polar solvent is a nitrile solvent. Preferably, the nitrile solvent is selected from one or more of acetonitrile and propionitrile. More preferably, the nitrile solvent is acetonitrile.

[0023] In some embodiments of the present invention, the aprotic polar solvent is a halogenated hydrocarbon solvent. Preferably, the halogenated hydrocarbon solvent is selected from one or more of dichloromethane, chloroform, and dichloroethane. More preferably, the halogenated hydrocarbon solvent is dichloromethane.

[0024] In some embodiments of the present invention, the aprotic polar solvent is a furan solvent. Preferably, the furan solvent is selected from one or more of tetrahydrofuran and 2-methyltetrahydrofuran. More preferably, the furan solvent is tetrahydrofuran.

[0025] In some embodiments of the present invention, the aprotic polar solvent is a ketone solvent. Preferably, the ketone solvent is selected from one or more of acetone and N-methylpyrrolidone.

[0026] In some embodiments of the present invention, the aprotic polar solvent is an amide solvent. Preferably, the amide solvent is selected from one or more of N,N-dimethylformamide and N,N-dimethylacetamide.

[0027] In some embodiments of the present invention, the elution mode of high performance liquid chromatography is isocratic elution.

[0028] In some embodiments of the present invention, the mobile phase of high performance liquid chromatography is a hydrocarbon solvent: an alcohol solvent: an amine solvent = (800 - 950):(100 - 200):(0.5 - 1.5) by volume ratio.

[0029] In some embodiments of the present invention, the hydrocarbon solvents forming the mobile phase are selected from n-pentane, cyclopentane, n-hexane, isohexane, cyclohexane, heptane, and diethyl ether; the alcohol solvents are selected from methanol, ethanol, n-propanol, isopropanol, n-butanol, and isobutanol; and the amine solvents are selected from triethylamine, diethylamine, butylamine, and ethanolamine.

[0030] In some embodiments of the present invention, the mobile phase of high performance liquid chromatography is n-hexane: ethanol: diethylamine = (800 - 950):(100 - 200):(0.5 - 1.5) by volume ratio.

[0031] In some embodiments of the present invention, the mobile phase of high performance liquid chromatography is n-hexane: ethanol: diethylamine = 850:150:1 by volume ratio.

[0032] In some embodiments of the present invention, the mobile phase of high performance liquid chromatography is an acid solvent: an amine solvent: a nitrile solvent: an alcohol solvent = (0.5 - 2.5):(1.5 - 3.5):(800 - 990):(15 - 25) by volume ratio.

[0033] In some embodiments of the present invention, the acid solvents forming the mobile phase are selected from formic acid, acetic acid, or phosphoric acid; the amine solvents are selected from triethylamine or diethylamine; the nitrile solvents are selected from acetonitrile or propionitrile; and the alcohol solvents are selected from methanol, ethanol, or isopropanol.

[0034] In some embodiments of the present invention, the mobile phase of high performance liquid chromatography is formic acid: diethylamine: acetonitrile: methanol = (0.5 - 2.5):(1.5 - 3.5):(800 - 990):(15 - 25) by volume ratio.

[0035] In some embodiments of the present invention, the mobile phase of high performance liquid chromatography is formic acid: diethylamine: acetonitrile: methanol = 1.9:2.6:980:20 by volume ratio.

[0036] In some embodiments of the present invention, the flow rate of high performance liquid chromatography is 0.5 - 2.0 ml / min.

[0037] In some embodiments of the present invention, the flow rate of high performance liquid chromatography is 1.0 - 1.8 ml / min.

[0038] In some embodiments of the present invention, the flow rate of high performance liquid chromatography is 1.5 - 1.8 ml / min.

[0039] In some embodiments of the present invention, the detection wavelength of high performance liquid chromatography is 205 - 326 nm.

[0040] In some embodiments of the present invention, the detection wavelength of high performance liquid chromatography is 240 - 280 nm.

[0041] In some embodiments of the present invention, the detection wavelength of high performance liquid chromatography is 254 nm.

[0042] In some embodiments of the present invention, the detection wavelength of high performance liquid chromatography is 264 nm.

[0043] In some embodiments of the present invention, the column temperature of high performance liquid chromatography is 20 - 35 °C.

[0044] In some embodiments of the present invention, the column temperature of high performance liquid chromatography is 30 °C.

[0045] In some embodiments of the present invention, the column temperature of high performance liquid chromatography is 20 °C.

[0046] The second aspect of the present invention provides an application of a furan solvent in the quality control research of a long-acting sustained-release preparation, characterized in that the furan solvent is tetrahydrofuran or 2-methyltetrahydrofuran.

[0047] In some embodiments of the present invention, the quality control research of the long-acting sustained-release preparation includes the following steps: (1) preparing a test solution by treating the long-acting sustained-release preparation with a furan solvent, and (2) performing separation and determination by normal-phase high performance liquid chromatography, wherein a chemically bonded chiral chromatographic column is selected as the chromatographic column.

[0048] In some embodiments of the present invention, the quality control study of the long-acting sustained-release preparation includes preparing a test solution by vortexing the long-acting sustained-release preparation with a furan solvent.

[0049] In some embodiments of the present invention, the chromatographic column is a polysaccharide derivative-bonded chiral chromatographic column.

[0050] In some embodiments of the present invention, the chromatographic column model is selected from DAICEL CHIRALPAK IA, DAICEL CHIRALPAK IB, DAICEL CHIRALPAK IC, DAICEL CHIRALPAK ID, DAICEL CHIRALPAK IE, DAICEL CHIRALPAK IF, DAICEL CHIRALPAK IG, DAICEL CHIRALPAK IH, DAICEL CHIRALPAK IJ, DAICEL CHIRALPAK IK, DAICEL CHIRALPAK IM.

[0051] In some embodiments of the present invention, the chromatographic column model is selected from DAICEL CHIRALPAK IA, DAICEL CHIRALPAK IB, DAICEL CHIRALPAK IC, DAICEL CHIRALPAK ID, DAICEL CHIRALPAK IE, DAICEL CHIRALPAK IF, DAICEL CHIRALPAK IG, DAICEL CHIRALPAK IH, DAICEL CHIRALPAK IJ, DAICEL CHIRALPAK IK, DAICEL CHIRALPAK IM, and the inner diameter of the chromatographic column is selected from 2.1 mm - 10 mm, the length is selected from 10 mm - 250 mm, and the particle size is selected from 1.6 μm - 10 μm;

[0052] In some embodiments of the present invention, the chromatographic column model is selected from DAICEL CHIRALPAK IA (4.6×250 mm, 5 μm), DAICEL CHIRALPAK IB (4.6×250 mm, 5 μm), DAICEL CHIRALPAK IC (4.6×250 mm, 5 μm).

[0053] In some embodiments of the present invention, the treatment with an organic solvent includes vortexing, ultrasonic treatment, or shaking treatment with an organic solvent.

[0054] In some embodiments of the present invention, the long-acting sustained-release preparation is a long-acting sustained-release microsphere preparation. Preferably, the long-acting sustained-release preparation is a long-acting sustained-release microsphere preparation of Compound I pamoate.

[0055] In some embodiments of the present invention, the furan solvent is selected from one or more of tetrahydrofuran and 2-methyltetrahydrofuran. More preferably, the furan solvent is tetrahydrofuran.

[0056] The present invention has the following beneficial effects:

[0057] 1. The analytical method of the present invention uses a chemically bonded chiral chromatographic column, which can effectively reduce interference during the detection process and has good compatibility with solvents and strong stability.

[0058] 2. The analytical method of the present invention can better achieve the separation effect of isomers in the raw materials and preparations of Compound I pamoate by selecting a more suitable organic solvent to treat the sample to be tested, compared with the use of commonly used solvents such as n-hexane, with high sensitivity and accuracy.

[0059] 3. The analytical method of the present invention is simple to operate, has a short analysis cycle, and has strong specificity, and can effectively control the isomers in the raw material and preparation of Compound I pamoate. BRIEF DESCRIPTION OF THE DRAWINGS

[0060] Figure 1 This is the normal phase-HPLC chromatogram of the test solution in Example 1;

[0061] Figure 2 This is the normal phase-HPLC chromatogram of the test solution in Example 2;

[0062] Figure 3 This is the normal phase-HPLC chromatogram of the test solution in Example 3;

[0063] Figure 4 This is the normal phase-HPLC chromatogram of the test solution of Example 4;

[0064] Figure 5 This is the normal phase-HPLC chromatogram of the test solution in Example 5;

[0065] Figure 6 This is the normal phase-HPLC chromatogram of the test solution of Comparative Example 1;

[0066] Figure 7 This is the normal phase-HPLC chromatogram of the test solution of Comparative Example 2;

[0067] Figure 8 The figure is the normal phase-HPLC chromatogram of the test solution of Comparative Example 3. DETAILED DESCRIPTION

[0068] The embodiments of the present invention will be described below, but the present invention is not limited thereto. The present invention is not limited to the respective configurations described below, and various modifications can be made within the scope of the claimed invention. Embodiments and examples obtained by appropriately combining the technical means disclosed in different embodiments and examples are also included in the technical scope of the present invention.

[0069] In addition, unless otherwise defined, other technical and scientific terms used in the present invention have the same meanings as those commonly understood by those of ordinary skill in the technical field to which the present invention belongs. Unless otherwise specified, the instruments, drugs, reagents, etc. used in the following examples can be obtained through conventional commercial means or prepared by known methods. For the experimental methods where specific conditions are not indicated in the examples, they are carried out under conventional conditions, such as the conditions described in the literature, books, or the methods recommended by the manufacturers.

[0070] The long-acting sustained-release microsphere preparation of compound I pamoate used in the following examples uses PLGA as a polymer and is prepared by the emulsion solvent evaporation method.

[0071] Example 1 - Detection of Isomers in the Bulk Drug of Compound I Pamoate

[0072] S1 Preparation of Test Solution

[0073] a. Take an appropriate amount of compound II, dissolve it with absolute ethanol, and dilute it with the mobile phase to prepare an isomer stock solution containing about 30 μg of compound II per 1 ml.

[0074] b. Take about 3 mg of the bulk drug of compound I pamoate, add 0.2 ml of the isomer stock solution and 0.8 ml of absolute ethanol, and mix well.

[0075] S2 Chromatographic Conditions

[0076] Chromatographic column: DAICEL CHIRALPAK IC, 4.6×250 mm, 5 μm;

[0077] Mobile phase: formic acid - diethylamine - acetonitrile - methanol (1.9:2.6:980:20), isocratic elution;

[0078] Flow rate: 1.0 ml / min;

[0079] Detection wavelength: 264 nm;

[0080] Injection volume: 10 μl.

[0081] S3 Detection Results

[0082] Take the test solution of S1 and use the chromatographic conditions in S2 to detect and record the chromatogram. The normal phase-HPLC chromatogram of the test solution of this embodiment is shown in Figure 1 , compound II is well separated from the main peak, and there is no interference in the peak position.

[0083] Example 2 - Detection of Isomers in the API of Compound I Pamoate

[0084] S1 Preparation of test solution

[0085] Same as Example 1.

[0086] S2 chromatographic conditions

[0087] Chromatographic column: DAICEL CHIRALPAK IA, 4.6 × 250 mm, 5 μm;

[0088] Mobile phase: n-hexane-ethanol-diethylamine (850:150:1), isocratic operation;

[0089] Flow rate: 1.5 ml / min;

[0090] Detection wavelength: 264nm;

[0091] Injection volume: 10 μl.

[0092] S3 test results

[0093] The normal phase-HPLC chromatogram of the test solution in this example is shown in Figure 2 , compound II is well separated from the main peak, and there is no interference in the peak position.

[0094] Example 3 - Detection of Isomers in a Formulation of Compound I Pamoate

[0095] S1 Preparation of test solution

[0096] a. Take an appropriate amount of Compound II, dissolve it in ethanol, and dilute it with the mobile phase to prepare a stock solution containing approximately 10 μg of the isomer of Compound II per 1 ml.

[0097] b. Accurately weigh approximately 20 mg of Compound I pamoate long-acting sustained-release microsphere injection, place in a 10-ml volumetric flask, add 0.5 ml of the isomer stock solution, evaporate the solvent, vortex with 1 ml of tetrahydrofuran, dilute to volume with mobile phase, mix, filter, and analyze the filtrate.

[0098] S2 chromatographic conditions

[0099] Chromatographic column: DAICEL CHIRALPAK IA, 4.6 × 250 mm, 5 μm;

[0100] Mobile phase: n-hexane - ethanol - diethylamine (850:150:1), isocratic elution;

[0101] Flow rate: 1.5 ml / min;

[0102] Detection wavelength: 254 nm;

[0103] Injection volume: 75 μl.

[0104] S3 Detection results

[0105] Take the test solution of S1 and detect it under the chromatographic conditions in S2, and record the chromatogram. The normal-phase high-performance liquid chromatogram of the test solution in this example is shown in Figure 3 , Compound II is well separated from the main peak, there is no interference at the peak position, and it is 0.205% calculated by the area normalization method, the extraction recovery rate is 101.9%, the limit of quantification is about 0.07 μg / ml, and the method has high sensitivity.

[0106] Example 4 - Detection of Isomers in the Preparation of Compound I Pamoate

[0107] On the basis of Example 3, use dichloromethane to replace tetrahydrofuran as the organic solvent for vortex treatment, and the remaining reagents, steps and conditions are the same as those in Example 3.

[0108] Detection results: The normal-phase high-performance liquid chromatogram of the test solution in this example is shown in Figure 4 , Compound II is well separated from the main peak, there is no interference at the peak position, and it is 0.191% calculated by the area normalization method, and the extraction recovery rate is 100.53%.

[0109] Example 5 - Detection of Isomers in the Preparation of Compound I Pamoate

[0110] On the basis of Example 3, use acetonitrile to replace tetrahydrofuran as the organic solvent for vortex treatment, and the remaining reagents, steps and conditions are the same as those in Example 3.

[0111] Detection results: The normal-phase high-performance liquid chromatogram of the test solution in this example is shown in Figure 5 , Compound II is well separated from the main peak, there is no interference at the peak position, and it is 0.173% calculated by the area normalization.

[0112] The above examples are method-validated, indicating that the detection method of the present invention has strong durability, good sensitivity and accuracy, and can better separate the isomers in compound I pamoate whether in the raw material drug or the preparation.

[0113] Comparative Example 1

[0114] In this example, the chromatographic column used was DAICEL CHIRALPAK AD-H, 4.6×250 mm, 5 μm, the detection wavelength was 254 nm, the injection volume was 75 μl, and the remaining reagents, steps and conditions were the same as those in Example 2.

[0115] Detection result: The normal-phase high-performance liquid chromatogram of the test solution in this example is shown in Figure 6 , and there was interference from pamoic acid at the peak position of Compound II.

[0116] Comparative Example 2

[0117] Based on Example 3, hexane was used to replace tetrahydrofuran as the organic solvent for vortex treatment, and the remaining reagents, steps and conditions were the same as those in Example 3.

[0118] Detection result: The normal-phase high-performance liquid chromatogram of the test solution in this example is shown in Figure 7 , and Compounds I and II could not be detected.

[0119] Comparative Example 3

[0120] Based on Example 3, dimethyl sulfoxide (DMSO) was used to replace tetrahydrofuran as the organic solvent for vortex treatment, and the remaining reagents, steps and conditions were the same as those in Example 3.

[0121] Detection result: The normal-phase high-performance liquid chromatogram of the test solution in this example is shown in Figure 8 , and there was solvent interference at the peak position of Compound II.

Claims

1. A method for analyzing isomers of benzothiazole compounds, characterized in that, The analysis method includes the following steps: (1) Take the test sample, treat it with an organic solvent, and prepare it into a test solution. The test sample contains the pamoate salt of compound I (S)-2-amino-4,5,6,7-tetrahydro-6-propylamine-benzothiazole; (2) Use normal-phase high-performance liquid chromatography for separation and determination, and select a chemically bonded chiral chromatographic column as the chromatographic column.

2. The method according to claim 1, characterized in that, The chromatographic column is a polysaccharide derivative-bonded chiral chromatographic column. Preferably, the chromatographic column model is selected from DAICEL CHIRALPAK IA, DAICEL CHIRALPAK IB, DAICEL CHIRALPAK IC, DAICEL CHIRALPAK ID, DAICEL CHIRALPAK IE, DAICEL CHIRALPAK IF, DAICEL CHIRALPAK IG, DAICEL CHIRALPAK IH, DAICEL CHIRALPAK IJ, DAICEL CHIRALPAK IK, DAICEL CHIRALPAK IM.

3. The method according to claim 1 or 2, characterized in that, The test sample is the bulk drug of the pamoate salt of compound I.

4. The method according to claim 3, characterized in that The organic solvent is selected from alcohol solvents, preferably one or more of methanol, ethanol, isopropanol or its isomers, n-butanol or its isomers.

5. The method according to claim 1 or 2, characterized in that, The test sample is a preparation of the pamoate salt of compound I. Preferably, the preparation is a long-acting sustained-release preparation. Preferably, the preparation is a long-acting sustained-release microsphere preparation.

6. The method according to claim 5, wherein The organic solvent is selected from aprotic polar solvents.

7. The method according to claim 6, wherein The aprotic polar solvent is selected from one or more of nitrile solvents, halogenated hydrocarbon solvents, furan solvents, ketone solvents, and amide solvents.

8. The method according to claim 7, characterized in that, The aprotic polar solvent is selected from one or more of acetonitrile, propionitrile, dichloromethane, dichloroethane, chloroform, tetrahydrofuran, 2-methyltetrahydrofuran, acetone, N-methylpyrrolidone, N,N-dimethylformamide, and N,N-dimethylacetamide.

9. The method according to any one of claims 1 to 8, characterized in that, The elution mode of high-performance liquid chromatography is isocratic elution, and the mobile phase is selected from: a. By volume ratio, hydrocarbon solvent: alcohol solvent: amine solvent = (800 - 950):(100 - 200):(0.5 - 1.5). Preferably, the hydrocarbon solvent is selected from n-pentane, cyclopentane, n-hexane, isohexane, cyclohexane, heptane, and diethyl ether; the alcohol solvent is selected from methanol, ethanol, n-propanol, isopropanol, n-butanol, and isobutanol; the amine solvent is selected from triethylamine, diethylamine, butylamine, and ethanolamine; or b. By volume ratio, acid solvent: amine solvent: nitrile solvent: alcohol solvent = (0.5 - 2.5):(1.5 - 3.5):(800 - 990):(15 - 25). Preferably, the acid solvent is selected from formic acid, acetic acid, or phosphoric acid; the amine solvent is selected from triethylamine or diethylamine; the nitrile solvent is selected from acetonitrile or propionitrile; the alcohol solvent is selected from methanol, ethanol, or isopropanol.

10. Application of a furan-based solvent in quality control of long-acting sustained-release preparations, characterized in that, The furan solvent is tetrahydrofuran or 2-methyltetrahydrofuran.

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