Method for detecting related substances in Ilaprazole drug

Abstract

The invention discloses a method for detecting related substances in an Ilaprazole drug. According to the method, by adjusting multiple parameters such as a chromatographic column, a flow phase, the pH value and the elution mode, impurities and a solvent peak can be completely separated, and the more impurities can be eluted; and the detection sensitivity of the method is greatly improved, and themethod is more suitable for quality detection in the production process.

Description

technical field

[0001] The invention relates to the technical field of drug quality control, in particular to a method for detecting related substances in ilaprazole. Background technique

[0002] Ilaprazole is the latest generation of proton pump inhibitor (PPI) developed and marketed by Livzon Group. It is widely used in various acid-related gastrointestinal diseases, such as duodenal ulcer, gastric ulcer, reflux Sexual esophagitis, etc. Compared with other PPIs, ilaprazole has the strongest antacid activity, no individual differences in treatment, and stronger ability to control acid at night, and is expected to become a core product in the PPI market.

[0003] Ilaprazole is easily destroyed in gastric acid. The related substance method of the current quality standard for Ilaprazole enteric-coated tablets is not sensitive to the detection of impurities, the number of impurities detected is small, the separation of impurities and solvent peaks is insufficient, and there a...

Examples

Embodiment 1

[0086] Get an appropriate amount of ilaprazole tablet fine powder (approximately equivalent to ilaprazole 15mg), put it in a 50ml measuring bottle, add solvent (600ml of 0.01mol / L dipotassium hydrogen phosphate solution and 400ml of acetonitrile and mix with 1mol / L hydroxide Sodium solution to adjust the pH value to 11.0 mixed solution, hereinafter referred to as solvent A) Appropriate amount, alternately dissolve by ultrasonic and shaking, each ultrasonic time is no more than 5 seconds, repeat 8-10 times, add solvent to dilute to the mark , shake well, filter, and take the continued filtrate as the test solution;

[0087] Precisely measure 1ml of the test solution, put it in a 100ml measuring bottle, dilute it to the mark with solvent A, shake it up, and use it as a reference solution; take 2-[[(4-methoxy-3-methyl)-2-pyridine Base]methyl]-sulfonyl-5-(1H-pyrrol-1-yl)-1H-benzimidazole (ilaprazole sulfone) about 5 mg, put it in a 100ml measuring bottle, add solvent A to dissolve...

Embodiment 2

[0100] Get 3 batches of ilaprazole tablets, each batch gets 2 groups, according to the method of embodiment 1 and comparative example 1 respectively, the detection of related substances is carried out to the test solution, and the results are shown in table 2.

[0101] Table 2 Test results of related substances

[0102]

[0103]Note: T means retention time (min), N.D means not detected.

[0104] The detection results show that under the same batch, the detection method of Example 1 detects more impurities and the number of impurities than Comparative Example 1, and has higher sensitivity, and is more suitable for the detection of related substances of the ilaprazole pharmaceutical composition.

Embodiment 3

[0105] Embodiment 3 chromatographic column screening

[0106] Get the test solution prepared in Example 1 and put it in a 90°C water bath to destroy it, and add 1ml of the ilaprazole sulfone reference substance solution prepared in Example 1, mix well, and use the mixed solution as the sample solution, according to Example 1 The method detects the related substance of sample solution, when detecting, uses different chromatographic columns (as shown in table 3), and detection result is shown in table 3.

[0107] Table 3 Test results of different chromatographic columns

[0108]

[0109] Note: R means resolution, T means retention time (min).

[0110] The results showed that when Gemini-NX C18 5μm (150×4.6mm), ACE Excel5 Super C18 1.7μm (150*4.6mm) and ECOSIL 120-5-C18 SH 5.0μm (150*4.6mm) were used as chromatographic columns, the impurities Most of the separation between the main peak and between impurities meets the requirements, and the number of detected impurities is...

technical field

[0001] The invention relates to the technical field of drug quality control, in particular to a method for detecting related substances in ilaprazole. Background technique

[0002] Ilaprazole is the latest generation of proton pump inhibitor (PPI) developed and marketed by Livzon Group. It is widely used in various acid-related gastrointestinal diseases, such as duodenal ulcer, gastric ulcer, reflux Sexual esophagitis, etc. Compared with other PPIs, ilaprazole has the strongest antacid activity, no individual differences in treatment, and stronger ability to control acid at night, and is expected to become a core product in the PPI market.

[0003] Ilaprazole is easily destroyed in gastric acid. The related substance method of the current quality standard for Ilaprazole enteric-coated tablets is not sensitive to the detection of impurities, the number of impurities detected is small, the separation of impurities and solvent peaks is insufficient, and there a...

Examples

Embodiment 1

[0086] Get an appropriate amount of ilaprazole tablet fine powder (approximately equivalent to ilaprazole 15mg), put it in a 50ml measuring bottle, add solvent (600ml of 0.01mol / L dipotassium hydrogen phosphate solution and 400ml of acetonitrile and mix with 1mol / L hydroxide Sodium solution to adjust the pH value to 11.0 mixed solution, hereinafter referred to as solvent A) Appropriate amount, alternately dissolve by ultrasonic and shaking, each ultrasonic time is no more than 5 seconds, repeat 8-10 times, add solvent to dilute to the mark , shake well, filter, and take the continued filtrate as the test solution;

[0087] Precisely measure 1ml of the test solution, put it in a 100ml measuring bottle, dilute it to the mark with solvent A, shake it up, and use it as a reference solution; take 2-[[(4-methoxy-3-methyl)-2-pyridine Base]methyl]-sulfonyl-5-(1H-pyrrol-1-yl)-1H-benzimidazole (ilaprazole sulfone) about 5 mg, put it in a 100ml measuring bottle, add solvent A to dissolve...

Embodiment 2

[0100] Get 3 batches of ilaprazole tablets, each batch gets 2 groups, according to the method of embodiment 1 and comparative example 1 respectively, the detection of related substances is carried out to the test solution, and the results are shown in table 2.

[0101] Table 2 Test results of related substances

[0102]

[0103]Note: T means retention time (min), N.D means not detected.

[0104] The detection results show that under the same batch, the detection method of Example 1 detects more impurities and the number of impurities than Comparative Example 1, and has higher sensitivity, and is more suitable for the detection of related substances of the ilaprazole pharmaceutical composition.

Embodiment 3

[0105] Embodiment 3 chromatographic column screening

[0106] Get the test solution prepared in Example 1 and put it in a 90°C water bath to destroy it, and add 1ml of the ilaprazole sulfone reference substance solution prepared in Example 1, mix well, and use the mixed solution as the sample solution, according to Example 1 The method detects the related substance of sample solution, when detecting, uses different chromatographic columns (as shown in table 3), and detection result is shown in table 3.

[0107] Table 3 Test results of different chromatographic columns

[0108]

[0109] Note: R means resolution, T means retention time (min).

[0110] The results showed that when Gemini-NX C18 5μm (150×4.6mm), ACE Excel5 Super C18 1.7μm (150*4.6mm) and ECOSIL 120-5-C18 SH 5.0μm (150*4.6mm) were used as chromatographic columns, the impurities Most of the separation between the main peak and between impurities meets the requirements, and the number of detected impurities is...

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