Method for resolution of R/S-lorcaserin by high performance liquid chromatography method

Abstract

The present invention belongs to the analytical chemistry field, and discloses a method for resolution of R / S-lorcaserin by a high performance liquid chromatography method. According to the present invention, the high performance liquid chromatography method is used, the amylose chiral column is adopted as the chromatographic column, and the n-hexane, the alcohol and the alkaline additive are adopted as the positive phase mobile phase. With the method of the present invention, the complete baseline separation of R / S-lorcaserin can be achieved, the good separation effect is provided, and the method can be used for the detection and the quality control of the lorcaserin bulk drug.

Description

technical field

[0001] The invention belongs to the field of analytical chemistry and relates to a method for splitting R / S-lorcaserin by using high performance liquid chromatography. Background technique

[0002] Lorcaserin is a new type of weight-loss drug that was approved for marketing by the U.S. Food and Drug Administration (FDA) on June 27, 2012. Its English name is Lorcaserin, and its chemical name is 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (8-chloro-1-methyl-2,3 ,4,5-tetrahydro-1H-3-benzazepin), the molecular formula is C11H15Cl2N 0.5H2O, the relative molecular mass is 195.69, and the structural formula is:

[0003]

[0004] Lorcaserin is a highly selective 5-hydroxytryptamine 2C receptor agonist that can regulate appetite and reduce food intake. It increases the activity of CNS serotonin through the stimulation of 5-HT2C receptors, activates the POMC system, and releases Melanocortin regulates heat balance, thereby affecting the descending pathwa...

Examples

Embodiment 1

[0052] Embodiment 1: the impact of diethylamine on separation effect

[0053] (1) Take 4mg each of R-lorcaserin and lorcaserin racemate, dissolve them in 1mL methanol solution, dilute 10 times with n-hexane, prepare a solution with a concentration of 400μg / mL, and then take 0.4mL R -Lorcaserin solution and 0.8mL lorcaserin racemate solution are mixed to obtain sample solution, and the content ratio of R-lorcaserin and S-lorcaserin in the solution is 2:1 this moment, then R -The ratio of the chromatographic peak area of ​​lorcaserin and S-lorcaserin should be 2:1;

[0054] (2) An Agilent 1260 high performance liquid chromatograph was used, with an amylose chiral column as the chromatographic column, and n-hexane, ethanol and diethylamine as the normal phase mobile phase. Control the flow rate of the mobile phase to 0.8mL / min, the detection wavelength to 270nm, the temperature of the chromatographic column oven to 35°C, and the injection volume to 10 μL, and adjust the ratio of...

Embodiment 2

[0062] Embodiment 2: the influence of mobile phase flow rate on separation effect

[0063] (1) Take 4 mg each of R-lorcaserin and lorcaserin racemate, dissolve them in 1 mL of methanol solution, dilute 10 times with n-hexane, prepare a solution with a concentration of 400 μg / mL, and then take 0.4 mL R-lorcaserin solution and 0.8mL lorcaserin racemate solution are mixed to obtain a sample solution, and now the content ratio of R-lorcaserin and S-lorcaserin in the solution is 2:1, then The ratio of the chromatographic peak area of ​​R-lorcaserin and S-lorcaserin should be 2:1;

[0064] (2) Agilent 1260 high performance liquid chromatography is adopted, with amylose chiral column as chromatographic column, n-hexane, ethanol and diethylamine as normal phase mobile phase, calculated by volume percentage, that is, n-hexane: ethanol: Diethylamine is 74.7%:25%:0.3%. The detection wavelength is 270nm, the temperature of the chromatographic column oven is 35°C, the injection volume is...

Embodiment 3

[0072] Example 3: The impact of the type and ratio of alcohol in the normal phase mobile phase on the separation effect

[0073] (1) Take 4mg each of R-lorcaserin and lorcaserin racemate, dissolve them in 1mL methanol solution, dilute 10 times with n-hexane, prepare a solution with a concentration of 400μg / mL, and then take 0.4mL R -Lorcaserin solution and 0.8mL lorcaserin racemate solution are mixed to obtain sample solution, and the content ratio of R-lorcaserin and S-lorcaserin in the solution is 2:1 this moment, then R -The ratio of the chromatographic peak area of ​​lorcaserin and S-lorcaserin should be 2:1;

[0074] (2) adopt Agilent 1260 high-performance liquid chromatograph, take amylose chiral column as chromatographic column, take n-hexane, alcohol and diethylamine as normal phase mobile phase, described alcohol is ethanol or isopropanol; control The flow rate of the mobile phase is 0.8mL / min, the detection wavelength is 270nm, the temperature of the chromatographic...

technical field

[0001] The invention belongs to the field of analytical chemistry and relates to a method for splitting R / S-lorcaserin by using high performance liquid chromatography. Background technique

[0002] Lorcaserin is a new type of weight-loss drug that was approved for marketing by the U.S. Food and Drug Administration (FDA) on June 27, 2012. Its English name is Lorcaserin, and its chemical name is 8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine (8-chloro-1-methyl-2,3 ,4,5-tetrahydro-1H-3-benzazepin), the molecular formula is C11H15Cl2N 0.5H2O, the relative molecular mass is 195.69, and the structural formula is:

[0003]

[0004] Lorcaserin is a highly selective 5-hydroxytryptamine 2C receptor agonist that can regulate appetite and reduce food intake. It increases the activity of CNS serotonin through the stimulation of 5-HT2C receptors, activates the POMC system, and releases Melanocortin regulates heat balance, thereby affecting the descending pathwa...

Examples

Embodiment 1

[0052] Embodiment 1: the impact of diethylamine on separation effect

[0053] (1) Take 4mg each of R-lorcaserin and lorcaserin racemate, dissolve them in 1mL methanol solution, dilute 10 times with n-hexane, prepare a solution with a concentration of 400μg / mL, and then take 0.4mL R -Lorcaserin solution and 0.8mL lorcaserin racemate solution are mixed to obtain sample solution, and the content ratio of R-lorcaserin and S-lorcaserin in the solution is 2:1 this moment, then R -The ratio of the chromatographic peak area of ​​lorcaserin and S-lorcaserin should be 2:1;

[0054] (2) An Agilent 1260 high performance liquid chromatograph was used, with an amylose chiral column as the chromatographic column, and n-hexane, ethanol and diethylamine as the normal phase mobile phase. Control the flow rate of the mobile phase to 0.8mL / min, the detection wavelength to 270nm, the temperature of the chromatographic column oven to 35°C, and the injection volume to 10 μL, and adjust the ratio of...

Embodiment 2

[0062] Embodiment 2: the influence of mobile phase flow rate on separation effect

[0063] (1) Take 4 mg each of R-lorcaserin and lorcaserin racemate, dissolve them in 1 mL of methanol solution, dilute 10 times with n-hexane, prepare a solution with a concentration of 400 μg / mL, and then take 0.4 mL R-lorcaserin solution and 0.8mL lorcaserin racemate solution are mixed to obtain a sample solution, and now the content ratio of R-lorcaserin and S-lorcaserin in the solution is 2:1, then The ratio of the chromatographic peak area of ​​R-lorcaserin and S-lorcaserin should be 2:1;

[0064] (2) Agilent 1260 high performance liquid chromatography is adopted, with amylose chiral column as chromatographic column, n-hexane, ethanol and diethylamine as normal phase mobile phase, calculated by volume percentage, that is, n-hexane: ethanol: Diethylamine is 74.7%:25%:0.3%. The detection wavelength is 270nm, the temperature of the chromatographic column oven is 35°C, the injection volume is...

Embodiment 3

[0072] Example 3: The impact of the type and ratio of alcohol in the normal phase mobile phase on the separation effect

[0073] (1) Take 4mg each of R-lorcaserin and lorcaserin racemate, dissolve them in 1mL methanol solution, dilute 10 times with n-hexane, prepare a solution with a concentration of 400μg / mL, and then take 0.4mL R -Lorcaserin solution and 0.8mL lorcaserin racemate solution are mixed to obtain sample solution, and the content ratio of R-lorcaserin and S-lorcaserin in the solution is 2:1 this moment, then R -The ratio of the chromatographic peak area of ​​lorcaserin and S-lorcaserin should be 2:1;

[0074] (2) adopt Agilent 1260 high-performance liquid chromatograph, take amylose chiral column as chromatographic column, take n-hexane, alcohol and diethylamine as normal phase mobile phase, described alcohol is ethanol or isopropanol; control The flow rate of the mobile phase is 0.8mL / min, the detection wavelength is 270nm, the temperature of the chromatographic...

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