A method for testing lansoprazole chloride in lansoprazole

Abstract

The invention belongs to the technical field of drug analysis, and specifically relates to a method for detecting lansoprazole chloride in lansoprazole. In order to solve the problem of detecting lansoprazole chloride in lansoprazole, a convenient, efficient and accurate detection method is provided. The method can detect the content of lansoprazole chloride in lansoprazole by liquid chromatography, thereby effectively ensuring the safety of drug use and facilitating the quality control of lansoprazole. The method is convenient, efficient and accurate, and fully complies with the guiding principles of method verification of the Chinese Pharmacopoeia in terms of system applicability, repeatability, specificity and accuracy, and can be used for the quality control of lansoprazole.

Description

Technical Field

[0001] The invention belongs to the technical field of drug analysis, and particularly relates to a method for testing lansoprazole chloride in lansoprazole. Background Art

[0002] Lansoprazole is a second-generation proton pump inhibitor developed and marketed by Takeda Pharmaceuticals of Japan. It has been among the top ten best-selling drugs in the world for several consecutive years. It inhibits the activity of the proton pump, H+ / K+-ATPase, of the gastric mucosal parietal cells, thereby inhibiting the secretion of gastric acid. It has a good therapeutic effect on gastric and duodenal ulcers and reflux esophagitis.

[0003] Lansoprazole chloride, chemical name: 2-chloromethyl-3-methyl-4-(2,2,2-trifluoroethoxy)pyridine hydrochloride, structural formula: , is the key intermediate in the synthesis of lansoprazole sulfide, the key starting material of lansoprazole. Lansoprazole chloride is a genotoxic impurity that may remain in the finished lansoprazole product. For the safety of the drug, it is very necessary to strictly control the content of lansoprazole chloride in lansoprazole.

[0004] The invention discloses a method for determining the content of lansoprazole chloride in lansoprazole by liquid chromatography, and provides a convenient, efficient and accurate detection method for solving the problem of detecting lansoprazole chloride in lansoprazole. The method can detect the content of lansoprazole chloride in lansoprazole, thereby effectively ensuring the safety of drug use and facilitating the quality control of lansoprazole. Summary of the invention

[0005] The invention provides a detection method for determining lansoprazole chloride in lansoprazole by liquid chromatography, and provides a convenient, efficient and accurate detection method to solve the detection problem of lansoprazole chloride in lansoprazole. The method can detect the content of lansoprazole chloride in lansoprazole, thereby effectively ensuring the safety of medication and facilitating the quality control of lansoprazole. The method is convenient, efficient and accurate, and fully complies with the guiding principles of method verification of the Chinese Pharmacopoeia in terms of system applicability, repeatability, specificity and accuracy, and can be used for the quality control of lansoprazole.

[0006] To achieve the above object, the present invention provides the following technical solutions: A method for testing lansoprazole chloride in lansoprazole, the method comprising the following steps: (1) Prepare solutions including blank solution, reference solution and test solution.

[0007] (2) Determination method: Use liquid chromatography to determine the content of lansoprazole chloride in lansoprazole. After the system is stable, add blank solution, reference solution and test solution respectively, and record the chromatogram; The chromatographic conditions are as follows: Detector: UV detector, chromatographic column: chromatographic column with octadecylsilane bonded silica as filler, injection volume: 35-45µl, column temperature: 40±5℃, flow rate: 1.0±0.1ml / min, ammonium acetate solution as mobile phase A, acetonitrile as mobile phase B, gradient elution.

[0008] Furthermore, the chromatographic column is YMC-Pack Pro C18, 4.6mm×150mm, 3µm.

[0009] Further, the elution gradient is: .

[0010] Further, the mobile phase A: weigh an appropriate amount of ammonium acetate, dissolve and dilute with water, and adjust the pH value to 6.4 with glacial acetic acid; For the blank solution: take an appropriate amount of sodium hydroxide solution, add diluent to dilute to the scale, and shake well; The volume ratio of the diluent: acetonitrile: water is 70:30; The reference substance solution: measure an appropriate amount of lansoprazole chloride reference substance into a volumetric flask, add an appropriate amount of sodium hydroxide solution, add diluent to dilute to the scale, and shake well; The test solution: measure an appropriate amount of lansoprazole test sample and place it in a volumetric flask, add an appropriate amount of sodium hydroxide solution, add diluent to dilute to the scale, and shake well.

[0011] The invention discloses a method for detecting lansoprazole chloride in lansoprazole, and provides a convenient, efficient and accurate detection method to solve the problem of detecting lansoprazole chloride in lansoprazole. The method can detect the content of lansoprazole chloride in lansoprazole, thereby effectively ensuring the safety of drug use. BRIEF DESCRIPTION OF THE DRAWINGS

[0012] Figure 1 This is the blank solution spectrum of lansoprazole chloride in lansoprazole Figure 2 Lansoprazole chloride reference solution in lansoprazole Figure 3 The selective solution spectrum of lansoprazole chloride in lansoprazole Figure 4 Spectrum of lansoprazole chloride test solution in lansoprazole DETAILED DESCRIPTION

[0013] The present invention is further illustrated by the following examples, but are not intended to limit the present invention.

[0014] Example 1: Determination of lansoprazole chloride in lansoprazole (1) Preparation of solution: Diluent: acetonitrile: water = 70:30 (V / V); Blank solution: Take a 20ml volumetric flask, add 0.4ml of 1mol / L NaOH solution, dilute to the scale with diluent, and shake well.

[0015] Lansoprazole chloride stock solution: weigh about 20 mg of lansoprazole chloride, accurately weigh it, place it in a 100 ml volumetric flask, add diluent to dissolve and dilute to the mark, shake well; accurately measure 5.0 ml of the above solution, place it in a 200 ml volumetric flask, add diluent to dilute to the mark, shake well. (Concentration: 5 μg / ml) Reference solution: Accurately measure 2.0 ml of lansoprazole chloride stock solution, place in a 20 ml volumetric flask, add 2 ml of diluent, add 0.4 ml of 1 mol / L NaOH solution, dilute to scale with diluent, and shake well. (Concentration: 0.5 μg / ml) Test solution (prepared for clinical use): Take about 200 mg of lansoprazole test sample, accurately weigh it, put it in a 10 ml volumetric flask, add 2 ml of diluent, add 0.2 ml of 1 mol / L NaOH solution to dissolve, add diluent to dilute to the scale, and shake well. (Concentration: 20 mg / ml) (2) Chromatographic conditions: Instrument: High performance liquid chromatograph equipped with UV detector, precision pH meter, electronic analytical balance; Chromatographic column: Use octadecylsilane bonded silica as filler (such as: YMC-Pack Pro C18 4.6×150mm, 3µm, or chromatographic column with equivalent performance) Flow rate: 1.0ml / min; Detection wavelength: 230nm; Injection volume: 40µl; Column temperature: 40℃; Autosampler temperature: 10℃; Mobile phase A: Weigh 0.77 g of ammonium acetate, dissolve in water and dilute to 1000 ml, adjust the pH to 6.4 with glacial acetic acid; Mobile phase B: acetonitrile; Gradient table:

[0016] (3) Steps After the system is stable, inject 1 injection of blank solution, 6 injections of reference solution, and 1 injection of test solution, and record the chromatogram.

[0017] Require 6. For the reference solution, the RSD calculated based on the lansoprazole chloride peak area should not be greater than 10.0%.

[0018] calculate Result (ppm) = (Ru / Rs) × (Cs / Cu) × 1000 Wherein: Ru: the peak area of ​​lansoprazole chloride in the spectrum of the test solution; Rs: average peak area of ​​lansoprazole chloride in 6 reference solutions; Cs: concentration of lansoprazole chloride in the reference solution (μg / ml); Cu: concentration of the test solution (mg / ml).

[0019] limit

[0020] The method for detecting lansoprazole chloride in lansoprazole also includes method validation before detection. The method validation is performed according to the chromatographic conditions of the formal detection, and the measurement results are as follows:

[0021] Example 2: System Applicability System suitability is achieved by measuring the RSD of the peak area of ​​lansoprazole chloride in the 6-pair reference solution. The RSD of the peak area of ​​lansoprazole chloride in the 6-pair reference solution should not be greater than 10.0%.

[0022]

[0023] Example 3: Specificity The specificity of the method is achieved by determining that the blank solution has no interference with the detection; the separation between lansoprazole chloride and adjacent peaks in the selective solution and the recovery rate of lansoprazole chloride before and after the addition of the sample. It is required that the blank solution should have no interference with the detection; the separation between lansoprazole chloride and adjacent peaks in the selective solution should be no less than 1.5; the recovery rate of lansoprazole chloride before and after the addition of the sample should be between 80.0% and 120.0%.

[0024]

[0025]

[0026] Example 4: Precision Precision is achieved by testing the RSD of the results of the six test solutions (spiked). The RSD of the results of the six test solutions (spiked) should not be greater than 10.0%.

[0027]

[0028] Example 5: Limit of Detection and Limit of Quantitation The limit of quantitation and the limit of detection are achieved by measuring the ratio of the detection response signal to the noise. The signal-to-noise ratio of the limit of quantitation is not less than 10:1, and the signal-to-noise ratio of the limit of detection is not less than 3:1. At the limit of quantitation concentration level, six minimum limit of quantitation solutions are repeatedly examined. 兰索拉唑氯化物 It should be no more than 25ppm, S / N≥10; the RSD of the peak area per unit concentration of lansoprazole chloride in 6 LOQ solutions should be no more than 10.0%, LOD≈1 / 3LOQ, S / N≥3.

[0029]

[0030]

[0031] Example 6: Linearity and Range In the concentration range of LOQ to 150%, take 5 concentration points and draw a curve with concentration as the horizontal axis and peak area as the vertical axis. It is required that the curve should be linear in the concentration range of LOQ to 150%, the square of the linear correlation coefficient R (R2) of the curve should be no less than 0.99, and the absolute value of the y-axis intercept should be within 25.0% of the 100% response value.

[0032]

[0033] Example 7: Accuracy The accuracy is achieved through the recovery rate between the measured concentration and the theoretical concentration of each component and the RSD of the recovery rate of each component. The recovery rate of lansoprazole chloride in the accuracy solution at each concentration point should be between 80.0% and 120.0%, and the RSD should not be greater than 10.0%.

[0034]

[0035] Example 8: Durability The reference solution, the test solution and the selective solution were placed at 10℃ for 20 hours* before injection, and the law of the change of the test results over time was investigated to provide a basis for the placement time of the reference solution and the test solution during the test. It is required that compared with 0 hours, the recovery rate of lansoprazole chloride of the reference solution placed at 10℃ for 20 hours should be between 90.0% and 110.0%, and the solution is stable; compared with 0 hours, the change value of the test result of the test solution placed at 10℃ for 20 hours is within 20% of the limit, and the solution is stable; the recovery rate of lansoprazole chloride of the selective solution placed at 10℃ for 20 hours should be between 80.0% and 120.0%, and the solution is stable.

[0036]

Claims

1. A method for testing lansoprazole chloride in lansoprazole, characterized in that: The inspection method comprises the following steps: (1) Prepare solutions, including blank solution, reference solution and test solution; (2) Determination method: Use liquid chromatography to determine the content of lansoprazole chloride in lansoprazole. After the system is stable, add blank solution, reference solution and test solution respectively, and record the chromatogram; The chromatographic conditions are as follows: Detector: UV detector, chromatographic column: chromatographic column with octadecylsilane bonded silica as filler, injection volume: 40±5µl, column temperature: 40±5℃, flow rate: 1.0±0.1ml / min, ammonium acetate solution as mobile phase A, acetonitrile as mobile phase B, gradient elution.

2. The inspection method according to claim 1, characterized in that: The chromatographic column is YMC-Pack Pro C18, 4.6 mm × 150 mm, 3 µm.

3. The inspection method according to claim 2, characterized in that: The elution gradient is: 。 4. The inspection method according to claim 3, characterized in that: Mobile phase A: weigh an appropriate amount of ammonium acetate, dissolve and dilute with water, and adjust the pH value to 6.0-7.0 with glacial acetic acid; For the blank solution: take an appropriate amount of sodium hydroxide solution, add diluent to dilute to the scale, and shake well; The diluent: The volume ratio of acetonitrile: water is 70:30; The reference substance solution: measure an appropriate amount of lansoprazole chloride reference substance into a volumetric flask, add an appropriate amount of sodium hydroxide solution, add diluent to dilute to the scale, and shake well; The test solution: measure an appropriate amount of lansoprazole test sample and place it in a volumetric flask, add an appropriate amount of sodium hydroxide solution, add diluent to dilute to the scale, and shake well.

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