Detection method of mosapride citrate isomer

Abstract

The invention provides a detection method of a mosapride citrate isomer, which comprises the following steps: taking a mosapride citrate test solution, injecting the mosapride citrate test solution into a liquid chromatograph, and detecting by adopting a liquid chromatography method in which n-hexane-isopropanol is taken as a mobile phase. The method provided by the invention is simple, convenient and rapid, has good separation degree and high detection efficiency, and can provide a method basis for research and control of the mosapride citrate isomer.

Description

Technical Field

[0001] The present invention relates to the technical field of drug detection, and in particular to a method for detecting mosapride citrate isomers. Background Art

[0002] Mosapride citrate is a selective 5-hydroxytryptamine (5-HT) receptor agonist. It promotes the release of acetylcholine by stimulating the 5-HT receptors of gastrointestinal cholinergic interneurons and intermuscular nerves, thereby enhancing gastrointestinal motility and improving gastrointestinal symptoms of patients with functional dyspepsia without affecting the secretion of gastric acid. As a gastrokinetic drug without dopamine receptor antagonism, mosapride citrate has the advantages of strong receptor selectivity, good pharmacokinetics, small dosage, safety, and high efficiency. Due to its good clinical efficacy and low side effects, it has been widely used at home and abroad, providing options and help for patients to relieve pain and restore health.

[0003] The structural formula of Mosapride Citrate is shown below:

[0004]

[0005] Its molecule contains chiral carbon atoms, so it exists as optical enantiomers and is currently used clinically in the form of a racemate.

[0006] As we all know, optical isomers with different chirality have great differences in pharmacology. The existence of optical isomers often affects the activity, bioavailability, metabolic rate and other aspects of the compound. In some cases, optical isomers may even produce unpredictable side effects. Therefore, in order to improve drug activity, reduce side effects, and conduct drug production and quality control, providing optically pure compounds has become a major issue in biochemistry and pharmacology.

[0007] At present, the detection method for the isomers of mosapride citrate is relatively complicated and is not suitable for simple sample detection. Therefore, seeking a detection method for the isomers of mosapride citrate that can effectively separate and is simple in method is of great significance for the quality control of mosapride citrate. Summary of the invention

[0008] Based on this, the present invention provides a method for detecting mosapride citrate isomers, which is simple, rapid, has good separation and high detection efficiency.

[0009] To achieve the above object, the present invention provides a method for detecting mosapride citrate isomers, comprising the following steps:

[0010] The mosapride citrate test solution was injected into a liquid chromatograph and detected by liquid chromatography, wherein n-hexane-isopropanol was used as the mobile phase.

[0011] The invention adopts n-hexane-isopropanol as the mobile phase and performs liquid chromatography detection on mosapride citrate, so that the two isomer peaks can achieve the best separation degree.

[0012] Preferably, the volume ratio of n-hexane to isopropanol is 85:15.

[0013] Preferably, the concentration of the mosapride citrate test solution is 1 mg / ml.

[0014] Preferably, in the present invention, the chromatographic column used in the liquid chromatography method is a polysaccharide derivative coated filler.

[0015] Preferably, the chromatographic column used in the liquid chromatography method is CHIRALPAK AD-H, 4.6×150 mm, 5 μm.

[0016] Preferably, the column temperature of the liquid chromatography is 30°C.

[0017] Preferably, the flow rate of the liquid chromatography is 0.4 ml / min.

[0018] Preferably, the detection wavelength of the liquid chromatography is 274 nm.

[0019] Preferably, the injection volume of the liquid chromatography method is 5 μl.

[0020] In the process of liquid chromatography detection of mosapride citrate, the present invention carries out multiple multi-factor tests, and the test results show that when the mobile phase is n-hexane-isopropanol (85:15), the separation degree of the two isomer peaks is the best, and when the mobile phase ratio is (50:50) and (70:30), the separation effect of the two isomer peaks is poor; when the concentration of the test solution is 1 mg / ml, the peak shape is excellent, and the separation degree of the two isomer peaks is the best, and when the concentration of the test solution is 2 mg / ml, the separation degree is slightly poor; when the flow rate is 0.4 ml / min, the peak elution time of the two isomer peaks is about 62-65 min, which is the most reasonable; when the flow rate is 0.3 ml / min, the peak elution time of the two isomer peaks is about 84-89 min, which is late and not conducive to detection.

[0021] Compared with the prior art, the present invention provides a method for detecting isomers of mosapride citrate, comprising the following steps: injecting a mosapride citrate test solution into a liquid chromatograph, and detecting by liquid chromatography, wherein n-hexane-isopropanol is used as a mobile phase. The method provided by the present invention is simple and rapid, has good separation and high detection efficiency, and can provide a method basis for the research and control of isomers of mosapride citrate. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0023] Figure 1 This is the HPLC spectrum of the test solution in Example 1;

[0024] Figure 2 This is the HPLC spectrum of the test solution of Example 2;

[0025] Figure 3 This is the HPLC spectrum of the test solution of Example 3;

[0026] Figure 4 This is the HPLC spectrum of the test solution of Example 4;

[0027] Figure 5 This is the HPLC spectrum of the test solution in Example 5. DETAILED DESCRIPTION

[0028] In the following specific implementations, the drugs, reagents and instruments used are as follows:

[0029] Mosapride citrate (homemade, batch number: 20230623); n-hexane (chromatographic grade, Rohn's reagent); isopropanol (chromatographic grade, MREDA); high performance liquid chromatograph (Dionex Technologies, USA); electronic balance (Mettler-Toledo Instruments (Shanghai) Co., Ltd., XSE205); chromatographic column (CHIRALPAK AD-H, 4.6×150 mm, 5 μm).

[0030] In the following examples, the ratios of solvents and liquids in the mobile phase are all by volume.

[0031] Example 1 Detection of Mosapride Citrate Isomers

[0032] Preparation of solvent: n-hexane-isopropanol (1:4)

[0033] Preparation of test sample solution: Accurately weigh about 10 mg of the test sample, accurately weigh it, place it in a 10 ml volumetric flask, add solvent to dissolve and dilute to the scale, shake well, and obtain.

[0034] HPLC detection conditions: mobile phase: n-hexane-isopropanol (85:15); column temperature 30°C, flow rate 0.4 ml / min, detection wavelength 274 nm; injection volume 5 μl.

[0035] Prepare the test solution according to the above method, inject it into the liquid chromatograph, and record the chromatogram. The results are as follows Figure 1 As shown, the two isomer peaks detected have the best separation, excellent peak shape, reasonable detection time, and the ratio of the two peaks is 1.00.

[0036] Example 2

[0037] Preparation of solvent: n-hexane-isopropanol (1:4)

[0038] Preparation of test sample solution: Accurately weigh about 20 mg of the test sample, accurately weigh it, place it in a 10 ml volumetric flask, add solvent to dissolve and dilute to the scale, shake well, and obtain.

[0039] HPLC detection conditions: mobile phase: n-hexane-isopropanol (50:50); column temperature 30°C, flow rate 1.0 ml / min, detection wavelength 274 nm; injection volume 5 μl.

[0040] Prepare the test solution according to the above method, inject it into the liquid chromatograph, and record the chromatogram. The results are as follows Figure 2 As shown, the two isomer peaks detected could not be separated by baseline.

[0041] Example 3

[0042] Preparation of solvent: n-hexane-isopropanol (1:4)

[0043] Preparation of test sample solution: Accurately weigh about 20 mg of the test sample, accurately weigh it, place it in a 10 ml volumetric flask, add solvent to dissolve and dilute to the scale, shake well, and obtain.

[0044] HPLC detection conditions: mobile phase: n-hexane-isopropanol (70:30); column temperature 30°C, flow rate 0.3 ml / min, detection wavelength 274 nm; injection volume 5 μl.

[0045] Prepare the test solution according to the above method, inject it into the liquid chromatograph, and record the chromatogram. The results are as follows Figure 3 As shown, the two isomer peaks detected cannot achieve baseline separation, and the separation degree is slightly better than that of Example 2.

[0046] Example 4

[0047] Preparation of solvent: n-hexane-isopropanol (1:4)

[0048] Preparation of test sample solution: Accurately weigh about 20 mg of the test sample, accurately weigh it, place it in a 10 ml volumetric flask, add solvent to dissolve and dilute to the scale, shake well, and obtain.

[0049] HPLC detection conditions: mobile phase: n-hexane-isopropanol (85:15); column temperature 30°C, flow rate 0.3 ml / min, detection wavelength 274 nm; injection volume 5 μl.

[0050] Prepare the test solution according to the above method, inject it into the liquid chromatograph, and record the chromatogram. The results are as follows Figure 4 As shown, the two isomer peaks detected are well separated, but the elution time is late (84-89 min), which is not conducive to sample detection.

[0051] Example 5

[0052] Preparation of solvent: n-hexane-isopropanol (1:4)

[0053] Preparation of test sample solution: Accurately weigh about 20 mg of the test sample, accurately weigh it, place it in a 10 ml volumetric flask, add solvent to dissolve and dilute to the scale, shake well, and obtain.

[0054] HPLC detection conditions: mobile phase: n-hexane-isopropanol (85:15); column temperature 30°C, flow rate 0.4 ml / min, detection wavelength 274 nm; injection volume 5 μl.

[0055] Prepare the test solution according to the above method, inject it into the liquid chromatograph, and record the chromatogram. The results are as follows Figure 5 As shown, the separation degree of the two isomer peaks detected is average, slightly worse than that of Example 1, and the ratio of the two peaks is 0.99.

[0056] The above embodiments are only used to help understand the method and core idea of ​​the present invention. It should be noted that, for those skilled in the art, several improvements and modifications can be made to the present invention without departing from the principles of the present invention, and these improvements and modifications also fall within the scope of protection of the claims of the present invention.

Claims

1. A method for detecting mosapride citrate isomers, comprising the following steps: The mosapride citrate test solution was injected into a liquid chromatograph and detected by liquid chromatography, wherein n-hexane-isopropanol was used as the mobile phase.

2. The method for detecting mosapride citrate isomers according to claim 1, wherein The volume ratio of n-hexane to isopropanol is 85:

15.

3. The method for detecting mosapride citrate isomers according to claim 1, characterized in that, The concentration of the mosapride citrate test solution is 1 mg / ml.

4. The method for detecting mosapride citrate isomers according to claim 1, wherein The chromatographic column used in the liquid chromatography method is a polysaccharide derivative coated filler.

5. The method for detecting mosapride citrate isomers according to claim 1, characterized in that, The chromatographic column used in the liquid chromatography method is CHIRALPAK AD-H, 4.6×150 mm, 5 μm.

6. The method for detecting mosapride citrate isomers according to claim 1, characterized in that: The column temperature of the liquid chromatography was 30°C.

7. The method for detecting mosapride citrate isomers according to claim 1, characterized in that: The flow rate of the liquid chromatography was 0.4 ml / min.

8. The method for detecting mosapride citrate isomers according to claim 1, characterized in that: The detection wavelength of the liquid chromatography is 274 nm.

9. The method for detecting mosapride citrate isomers according to claim 1, characterized in that: The injection volume for the liquid chromatography was 5 μl.

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