Method for detecting related substances of compound sodium picosulfate oral solution

Abstract

The invention relates to the technical field of pharmaceutical analysis, in particular to a method for detecting related substances of a compound sodium picosulfate oral solution. According to the method, high performance liquid chromatography is adopted for detection, a chromatographic column is a bonded silica gel reversed-phase chromatographic column, a mobile phase A is a dipotassium phosphate buffer solution, a mobile phase B is acetonitrile, and gradient elution is adopted. The method can effectively detect related substances in the compound sodium picosulfate oral solution, has the advantages of strong specificity, high sensitivity and the like, has good detection capability on specific impurities in the compound sodium picosulfate oral solution, and effectively guarantees the quality of the compound sodium picosulfate oral solution.

Description

Technical Field

[0001] The invention belongs to the field of drug analysis, and in particular relates to a method for detecting related substances in a compound sodium picosulfate oral solution. Background Art

[0002] Compound Sodium Picosulfate Oral Solution is an intestinal cleansing drug. Its main ingredients are sodium picosulfate, magnesium oxide and anhydrous citric acid. It is a compound preparation. The chemical name of sodium picosulfate is 4,4'-[(pyridin-2-yl)methylene]diphenylbis(sodium sulfate) monohydrate, and its chemical structure is: .

[0003] The dosage forms of compound sodium picosulfate mainly include: compound sodium picosulfate granules, compound sodium picosulfate oral solution, etc.; it is used for intestinal cleansing preparation before colonoscopy and X-ray examination.

[0004] Among them, compound sodium picosulfate oral solution has irreplaceable advantages in clinical practice due to its flexible dosage, good taste and good compliance.

[0005] The European Pharmacopoeia lists three known impurities (impurities A, B, and C) in sodium picosulfate raw materials. Compound sodium picosulfate oral solution has the characteristics of more excipients and complex related substances. In addition to the process impurities and degradation impurities of the sodium picosulfate raw materials themselves, attention should also be paid to the peak elution of excipients.

[0006] At present, the mainstream pharmacopoeias of various countries do not include compound sodium picosulfate oral solution, and there is no detection method for related substances of compound sodium picosulfate oral solution. The detection method of related substances of sodium picosulfate raw materials has the risk of missing the detection of oral solution-specific impurities or poor specificity. It is urgent to develop a detection method for related substances of compound sodium picosulfate oral solution. Summary of the invention

[0007] Purpose of the invention: The purpose of the present invention is to provide a detection method that can detect related substances in compound sodium picosulfate oral solution, including impurities (impurities A, B, C) included in the pharmacopoeias of various countries for compound sodium picosulfate.

[0008] The object of the present invention is achieved by the following technical scheme: a method for detecting related substances of compound sodium picosulfate oral solution, characterized in that high performance liquid chromatography is used for detection, the chromatographic column is a reverse phase chromatographic column of bonded silica gel, the mobile phase A is a dipotassium hydrogen phosphate buffer, the mobile phase B is acetonitrile, and the mobile phase elution gradient is as follows: Time (minutes) Mobile phase A (%) Mobile phase B (%) 0 90 10 15 70 30 25 70 30 25.1 30 70 30 30 70 30.1 90 10 35 90 10 .

[0009] The filler of the chromatographic column is octylsilane bonded silica gel or octadecylsilane bonded silica gel.

[0010] The filler of the chromatographic column is preferably octadecylsilane bonded silica gel.

[0011] The mobile phase A is prepared by the following method: 1.57 g to 1.91 g of dipotassium hydrogen phosphate is weighed, dissolved in water and diluted to 1000 ml, and the pH is adjusted to 6.3 to 6.5 with phosphoric acid solution.

[0012] The mobile phase A is preferably prepared by the following method: weigh 1.74 g of dipotassium hydrogen phosphate, dissolve it in water and dilute it to 1000 ml, and adjust the pH to 6.4 with phosphoric acid solution.

[0013] Other chromatographic conditions of the high performance liquid chromatography method are: column temperature of 30°C to 50°C, injection volume of 50 to 100 μl, mobile phase flow rate of 0.8 to 1.2 ml / min, and detection wavelength of 261 to 265 nm.

[0014] Other chromatographic conditions of the HPLC method are as follows: column temperature is 45° C., injection volume is 100 μl, mobile phase flow rate is 1.0 ml / min, and detection wavelength is 263 nm.

[0015] The present invention has the positive effects that the detection method of the present invention can effectively detect the related substances of the compound sodium picosulfate oral solution, has the advantages of strong specificity, high sensitivity, etc., and has good detection ability for the specific impurities of the compound sodium picosulfate oral solution, effectively ensuring the quality of the compound sodium picosulfate oral solution. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] Figure 1 It is the structural formula of impurity A.

[0017] Figure 2 It is the structural formula of impurity B.

[0018] Figure 3 It is the structural formula of impurity C.

[0019] Figure 4 It is the chromatogram of blank auxiliary material solution of Example 1.

[0020] Figure 5 This is the solution chromatogram of the system suitability of Example 1.

[0021] Figure 6 This is the chromatogram of the sample solution in Example 1.

[0022] Figure 7 It is the chromatogram of blank auxiliary material solution of Example 2.

[0023] Figure 8 This is the solution chromatogram of the system suitability of Example 2.

[0024] Fig. 9 This is the chromatogram of the sample solution of Example 2.

[0025] Fig.10 This is the chromatogram of the spiked solution of the test sample in Example 3. DETAILED DESCRIPTION

[0026] The present invention is further described in detail below in conjunction with examples, but the embodiments of the present invention are not limited thereto.

[0027] Example 1 A method for detecting related substances in compound sodium picosulfate oral solution, the chromatographic conditions of which are shown in Table 1.

[0028] Table 1 Chromatographic conditions of Example 1 Chromatographic columns Horizon C18, 4.6mm×250mm, 5μm Mobile phase A 0.01 mol / L potassium dihydrogen phosphate buffer (adjust pH to 6.4 with phosphoric acid) Mobile phase B Acetonitrile Elution gradient Time (min) Mobile phase A (%) Mobile phase B (%) 0901015703025703025.1307030307030.19010359010 Flow rate 1.0ml / min Column temperature 45℃ Injection volume 100μl Detection wavelength 263nm System suitability solution preparation Take an appropriate amount of impurity A reference substance, accurately weigh it, add solvent to dissolve it and quantitatively dilute it to make a solution containing about 0.1 mg per 1 ml, as the stock solution of impurity A; prepare the stock solution of impurity C in the same way; take an appropriate amount of impurity B reference substance, accurately weigh it, add a small amount of acetonitrile to dissolve it and quantitatively dilute it with solvent to make a solution containing about 0.1 mg per 1 ml, as the stock solution of impurity B; take an appropriate amount of sodium picosulfate, accurately weigh it, add an appropriate amount of solvent to dissolve it, then accurately measure an appropriate amount of the above-mentioned impurity stock solutions, dilute them with solvent to make a mixed solution containing about 57 μg of sodium picosulfate and 1 μg of each impurity per 1 ml, and shake well. Preparation of test solution Take an appropriate amount of compound sodium picosulfate oral solution. Preparation of blank excipient solution Take an appropriate amount of blank auxiliary material solution to obtain the product. .

[0029] The experimental results of Example 1 are shown in Table 2.

[0030] Table 2 Experimental results of the examples Experimental solution Experimental Results Attached photos Blank excipient solution The chromatographic peaks of the blank excipient solution did not interfere with the detection of impurity peaks in the compound sodium picosulfate oral solution sample. Figure 4 System Suitability Solutions In the system suitability solution chromatogram, sodium picosulfate, impurity C, impurity A and impurity B appeared in sequence, and the separation between the peaks was greater than 1.5. Figure 5 Sample solution Only impurity A was detected in compound sodium picosulfate oral solution, with the contents as follows: Impurity A: 0.05% Impurity B: Not detected Impurity C: Not detected Maximum unknown single impurity: 0.07% Total impurities: 0.17% Figure 6 .

[0031] Example 2 A method for detecting related substances in compound sodium picosulfate oral solution (placed under high temperature conditions for 30 days), wherein the chromatographic conditions are shown in Table 3.

[0032] Table 3 Chromatographic conditions of Example 2 Chromatographic columns Horizon C18, 4.6mm×250mm, 5μm Mobile phase A 0.01 mol / L potassium dihydrogen phosphate buffer (adjust pH to 6.4 with phosphoric acid) Mobile phase B Acetonitrile Elution gradient Time (min) Mobile phase A (%) Mobile phase B (%) 0901015703025703025.1307030307030.19010359010 Flow rate 1.0ml / min Column temperature 45℃ Injection volume 100μl Detection wavelength 263nm System suitability solution preparation Take an appropriate amount of impurity A reference substance, accurately weigh it, add solvent to dissolve it and quantitatively dilute it to make a solution containing about 0.1 mg per 1 ml, as the stock solution of impurity A; prepare the stock solution of impurity C in the same way; take an appropriate amount of impurity B reference substance, accurately weigh it, add a small amount of acetonitrile to dissolve it and quantitatively dilute it with solvent to make a solution containing about 0.1 mg per 1 ml, as the stock solution of impurity B; take an appropriate amount of sodium picosulfate, accurately weigh it, add an appropriate amount of solvent to dissolve it, then accurately measure an appropriate amount of the above-mentioned impurity stock solutions, dilute them with solvent to make a mixed solution containing about 57 μg of sodium picosulfate and 1 μg of each impurity per 1 ml, and shake well. Sample solution preparation Take an appropriate amount of compound sodium picosulfate oral solution. Preparation of blank excipient solution Take an appropriate amount of blank auxiliary material solution to obtain the product. .

[0033] The experimental results of Example 2 are shown in Table 4.

[0034] Table 4 Experimental results of the examples Experimental solution Experimental Results Attached photos Blank excipient solution The chromatographic peaks of the blank excipient solution did not interfere with the detection of impurity peaks in the compound sodium picosulfate oral solution sample. Figure 7 System Suitability Solutions In the system suitability solution chromatogram, sodium picosulfate, impurity C, impurity A and impurity B appeared in sequence, and the separation between the peaks was greater than 1.5. Figure 8 Sample solution Impurity A and impurity B were detected in compound sodium picosulfate oral solution, and the contents were: Impurity A: 5.4% Impurity B: 0.06% Impurity C: Not detected Maximum unknown single impurity: 0.28% Total impurities: 5.9% Figure 7 .

[0035] Example 3 Comparative Examples 1-3: The chromatographic conditions of each comparative example are substantially the same as those of Example 1, except for the initial ratio of the mobile phase gradient elution.

[0036] The initial ratio of the mobile phase in Comparative Example 1 was 90:10.

[0037] The initial ratio of the mobile phase in Comparative Example 2 was 92:8.

[0038] The initial ratio of the mobile phase in Comparative Example 3 was 88:12.

[0039] Depend on Fig.10 It can be seen that the initial ratio of the mobile phase affects the separation of the impurity C and the auxiliary material peak of this product. When the initial ratio of the mobile phase is 92:8, the separation degree between the impurity C and the auxiliary material peak becomes smaller; when the initial ratio of the mobile phase is 88:12, the separation degree between the impurity C and the auxiliary material peak becomes larger; at the same time, in order to ensure the separation between other impurities and auxiliary materials, the organic phase ratio is controlled in the range of 8%-12%.

Claims

1. A method for detecting related substances in compound sodium picosulfate oral solution, It is characterized in that High performance liquid chromatography was used for detection. The chromatographic column was a reverse phase column bonded with silica gel. Mobile phase A was dipotassium hydrogen phosphate buffer, mobile phase B was acetonitrile, and the mobile phase elution gradient was as follows: 。 2. The method according to claim 1, Features The filler of the chromatographic column is octylsilane bonded silica gel or octadecylsilane bonded silica gel.

3. The method according to claim 2, Features The filler of the chromatographic column is octadecylsilane bonded silica gel.

4. The method according to claim 1, Features The mobile phase A is prepared by the following method: 1.57 g to 1.91 g of dipotassium hydrogen phosphate is weighed, dissolved in water and diluted to 1000 ml, and the pH is adjusted to 6.3 to 6.5 with phosphoric acid solution.

5. The method according to claim 4, Features The mobile phase A was prepared by the following method: 1.74 g of dipotassium hydrogen phosphate was weighed, dissolved in water and diluted to 1000 ml, and the pH was adjusted to 6.4 with phosphoric acid solution.

6. The method according to claim 1, Features Other chromatographic conditions of the high performance liquid chromatography method are: column temperature of 30°C to 50°C, injection volume of 50 to 100 μl, mobile phase flow rate of 0.8 to 1.2 ml / min, and detection wavelength of 261 to 265 nm.

7. The method according to claim 6, Features Other chromatographic conditions of the HPLC method are as follows: column temperature is 45° C., injection volume is 100 μl, mobile phase flow rate is 1.0 ml / min, and detection wavelength is 263 nm.

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