A kind of method for determining degradation impurities in orlistat capsules

Abstract

The invention discloses a method for measuring degraded impurities in orlistat capsules and relates to the field of analytical chemistry.According to the method, a high performance liquid chromatographic method is adopted, an impurity mixed reference substance solution and a sample solution are injected in a high performance liquid chromatograph, and measurement of the degraded impurities in the orlistat capsules is completed.According to the chromatographic conditions, silica gel solid sphere particles are used as filler of a chromatographic column; a mobile phase A is an acidic water solution, a mobile phase B is an organic solvent, the sum of the percent by volume of the mobile phase A and the percent by volume of the mobile phase B is kept 100% all the time, and linear gradient elution is carried out.According to the method, the Cortecs C18 (Waters, 150 mm*4.6 mm, 2.7 micrometers) chromatographic column is adopted, and by optimizing the mobile phase gradient elution procedure, all the degraded impurities and process impurities hard to separate nearby a main peak can be separated under the same chromatographic conditions, and the degraded impurities in the orlistat capsules can be effectively detected.

Description

technical field

[0001] The invention relates to the field of analytical chemistry, in particular to a method for separating and measuring degraded impurities in orlistat capsules by commonly used high-performance liquid chromatography. Background technique

[0002] Orlistat was first discovered in 1987. The chemical name of Orlistat (Orlistat) is: (s)-2-formamido-4-methyl-pentanoic acid (s)-1-[[(2s, 3s )-3-hexyl-4-oxo-2oxetany]methyl-dodecyl ester, the chemical formula of which is as follows. The trade name is Xenical, which was developed by Hoffmann-La Roche in Switzerland. It was first launched in New Zealand in 1998 and in the United States in 1999. Orlistat, as a potent and long-acting gastrointestinal lipase inhibitor, is a new type of weight loss drug with non-systemic effect, good tolerance and effectiveness. Treating obesity without appetite suppressants opens up new avenues for pharmacological treatment of obesity.

[0003]

[0004] The degradation impurities ...

Examples

preparation example Construction

[0043] Preparation of disruption solution:

[0044] ①. Orlistat stock solution: take an appropriate amount of orlistat capsule content powder, add acetonitrile-water mixed solution with a volume ratio of 4:1 to make a 0.5 mg / mL solution, and obtain it.

[0045] ②. Hydrochloric acid methanol destruction solution: Take an appropriate amount of orlistat capsule content powder, which is equivalent to 50 mg of orlistat, put it in a 100mL measuring bottle, add a mixed solution of methanol-water volume ratio 4:1, ultrasonically shake, Completely dissolve orlistat, add 5mL of 0.1mol / L hydrochloric acid, let stand at room temperature for 1 hour, add 5mL of 0.1mol / L sodium hydroxide solution for neutralization, and mix the solvent with a mixed solution of methanol-water volume ratio 4:1 Dilute to the mark, that is.

[0046] ③. Hydrochloric acid ethanol destruction solution: Take an appropriate amount of orlistat capsule content powder, which is equivalent to 50mg orlistat, put it in a ...

Embodiment 1

[0053] Embodiment 1: System suitability test

[0054] Instruments and experimental conditions:

[0055] High performance liquid chromatography: Shimadzu LC-16;

[0056] Chromatographic column: Cortecs C 18 (Waters, 150×4.6mm, 2.7μm);

[0057] Mobile phase A is 0.025% by volume phosphoric acid aqueous solution, and mobile phase B is acetonitrile; linear gradient elution according to Table 2.

[0058]

[0059]

[0060] The flow rate is 1.3mL / min;

[0061] Column temperature 35°C;

[0062] Detection wavelength 195nm;

[0063] The injection volume was 20 μl.

[0064] Experimental steps:

[0065] Take acetonitrile-water volume ratio is 4: 1 mixed solution and impurity mixed reference substance solution respectively, carry out high performance liquid chromatography analysis according to above-mentioned experimental conditions, record chromatogram, the result sees figure 1 , figure 2 , ORL in the figure represents orlistat. figure 2 The middle is the chromatogram co...

Embodiment 2

[0069] Embodiment 2: system suitability comparative test (USP37 method)

[0070] Instruments and experimental conditions:

[0071] High performance liquid chromatography: Shimadzu LC-16;

[0072] Chromatographic column: Nova-pak C18 (3.9mm×150mm, 4.0μm);

[0073] Mobile phase: acetonitrile-phosphoric acid-water mixed solution with a volume ratio of 88:0.05:12;

[0074] Flow rate: 1.0mL / min;

[0075] Column temperature: 35°C;

[0076] Wavelength: 195nm;

[0077] Injection volume: 20 μl.

[0078] Experimental steps:

[0079] Get impurity mixed reference substance solution, carry out high performance liquid chromatography analysis according to above-mentioned experimental conditions, record chromatogram, the result sees image 3 And Table 4, it can be found that in the method of the USP 37th edition, orlistat is not separated from the ring opener methyl ester at all, and the peaks of each impurity are relatively close, which is not conducive to separation. Therefore, th...

technical field

[0001] The invention relates to the field of analytical chemistry, in particular to a method for separating and measuring degraded impurities in orlistat capsules by commonly used high-performance liquid chromatography. Background technique

[0002] Orlistat was first discovered in 1987. The chemical name of Orlistat (Orlistat) is: (s)-2-formamido-4-methyl-pentanoic acid (s)-1-[[(2s, 3s )-3-hexyl-4-oxo-2oxetany]methyl-dodecyl ester, the chemical formula of which is as follows. The trade name is Xenical, which was developed by Hoffmann-La Roche in Switzerland. It was first launched in New Zealand in 1998 and in the United States in 1999. Orlistat, as a potent and long-acting gastrointestinal lipase inhibitor, is a new type of weight loss drug with non-systemic effect, good tolerance and effectiveness. Treating obesity without appetite suppressants opens up new avenues for pharmacological treatment of obesity.

[0003]

[0004] The degradation impurities ...

Examples

preparation example Construction

[0043] Preparation of disruption solution:

[0044] ①. Orlistat stock solution: take an appropriate amount of orlistat capsule content powder, add acetonitrile-water mixed solution with a volume ratio of 4:1 to make a 0.5 mg / mL solution, and obtain it.

[0045] ②. Hydrochloric acid methanol destruction solution: Take an appropriate amount of orlistat capsule content powder, which is equivalent to 50 mg of orlistat, put it in a 100mL measuring bottle, add a mixed solution of methanol-water volume ratio 4:1, ultrasonically shake, Completely dissolve orlistat, add 5mL of 0.1mol / L hydrochloric acid, let stand at room temperature for 1 hour, add 5mL of 0.1mol / L sodium hydroxide solution for neutralization, and mix the solvent with a mixed solution of methanol-water volume ratio 4:1 Dilute to the mark, that is.

[0046] ③. Hydrochloric acid ethanol destruction solution: Take an appropriate amount of orlistat capsule content powder, which is equivalent to 50mg orlistat, put it in a ...

Embodiment 1

[0053] Embodiment 1: System suitability test

[0054] Instruments and experimental conditions:

[0055] High performance liquid chromatography: Shimadzu LC-16;

[0056] Chromatographic column: Cortecs C 18 (Waters, 150×4.6mm, 2.7μm);

[0057] Mobile phase A is 0.025% by volume phosphoric acid aqueous solution, and mobile phase B is acetonitrile; linear gradient elution according to Table 2.

[0058]

[0059]

[0060] The flow rate is 1.3mL / min;

[0061] Column temperature 35°C;

[0062] Detection wavelength 195nm;

[0063] The injection volume was 20 μl.

[0064] Experimental steps:

[0065] Take acetonitrile-water volume ratio is 4: 1 mixed solution and impurity mixed reference substance solution respectively, carry out high performance liquid chromatography analysis according to above-mentioned experimental conditions, record chromatogram, the result sees figure 1 , figure 2 , ORL in the figure represents orlistat. figure 2 The middle is the chromatogram co...

Embodiment 2

[0069] Embodiment 2: system suitability comparative test (USP37 method)

[0070] Instruments and experimental conditions:

[0071] High performance liquid chromatography: Shimadzu LC-16;

[0072] Chromatographic column: Nova-pak C18 (3.9mm×150mm, 4.0μm);

[0073] Mobile phase: acetonitrile-phosphoric acid-water mixed solution with a volume ratio of 88:0.05:12;

[0074] Flow rate: 1.0mL / min;

[0075] Column temperature: 35°C;

[0076] Wavelength: 195nm;

[0077] Injection volume: 20 μl.

[0078] Experimental steps:

[0079] Get impurity mixed reference substance solution, carry out high performance liquid chromatography analysis according to above-mentioned experimental conditions, record chromatogram, the result sees image 3 And Table 4, it can be found that in the method of the USP 37th edition, orlistat is not separated from the ring opener methyl ester at all, and the peaks of each impurity are relatively close, which is not conducive to separation. Therefore, th...

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