Analysis method of chiral isomer

An isomer and volume technology, applied in the field of analysis of pharmaceutical raw materials, can solve the problems of not mentioning the separation of diastereomers, not being able to detect three isomers at the same time, and not realizing baseline separation, etc. Ease of standardization, method specificity and reproducibility, and good separation

Pending Publication Date: 2019-01-18
药源生物科技(启东)有限公司
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  • Abstract
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Problems solved by technology

Therefore, the method is cumbersome to operate and cannot achieve the purpose of simultaneously detecting three isomers
[0006] Invention patent CN200810118823.9 reports a chiral method, using a chiral column CHIROBIOTIC with a macrocyclic glycopeptide teicoplanin (Teicoplanin) bonded to silica gel as a filler, which can separate four configurations, but these four configurations Baseline separation is not achieved
[0007] Invention patent CN200910117598.1 reported the analysis method of separating enantiomers using AS-H chiral column, n-hexane-isopropanol-diethylamine mixed solvent as mobile phase, but did not mention the other two Separation of Enantiomers
However, the detection time of this method is long, and one needle needs at least 110 minutes, and because the retention time of the isomer is too long, the peak width is wider at about 100 minutes, resulting in poor sensitivity of the method

Method used

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  • Analysis method of chiral isomer
  • Analysis method of chiral isomer
  • Analysis method of chiral isomer

Examples

Experimental program
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Effect test

Embodiment 1

[0039] Resolution solution: A mixed solution containing palonosetron hydrochloride and 3 isomers was prepared with ethanol, with a concentration of 0.25 mg / ml, respectively.

[0040] HPLC operating conditions: chiral column (DAICEL CHIRALPAK AD-H 250×4.6mm, 5μm) with tris(3,5-dimethylphenylcarbamate) amylose as filler, n-hexane-ethanol -Methanol-trifluoroacetic acid-diethylamine (volume ratio=75:20:5:0.2:0.1) as mobile phase; flow rate is 1ml / min; column temperature is 35℃; detection wavelength is 240nm; injection volume is 5μL .

[0041] Take the resolution solution and inject it into the liquid chromatograph to get the attached solution. figure 1 chromatogram shown. S, R, R, R, R, S isomers and palonosetron hydrochloride appeared successively, and the retention times were 7.5 min, 8.5 min, 10.6 min and 13.7 min, respectively.

Embodiment 2

[0043]Resolution solution: A mixed solution containing palonosetron hydrochloride and 3 isomers was prepared with ethanol, with a concentration of 0.25 mg / ml, respectively.

[0044] HPLC operating conditions: chiral column (DAICEL CHIRALPAK AD-H 250×4.6mm, 5μm) with tris(3,5-dimethylphenylcarbamate) amylose as filler, n-hexane-ethanol -Methanol-trifluoroacetic acid-diethylamine (volume ratio=70:25:5:0.2:0.1) as mobile phase; flow rate is 1ml / min; column temperature is 35℃; detection wavelength is 240nm; injection volume is 5μL .

[0045] Take the resolution solution and inject it into the liquid chromatograph to get the attached solution. figure 2 chromatogram shown. S, R, R, R, R, S isomers and palonosetron hydrochloride appeared successively, and the retention times were 6.8 min, 7.4 min, 9.1 min and 11.8 min, respectively.

Embodiment 3

[0047] Control solution: Precisely weigh appropriate amount of Palonosetron hydrochloride and 3 isomer reference substances, dissolve in methanol, and prepare 0.5 μg / ml with diluent (methanol-mobile phase (volume ratio = 1:9)). mixture.

[0048] Test solution: take an appropriate amount of palonosetron hydrochloride, and prepare a solution of 5 mg / ml with diluent (methanol-mobile phase (volume ratio=1:9)).

[0049] HPLC operating conditions: chiral column (DAICEL CHIRALPAK AD-H 250×4.6mm, 5μm) with tris(3,5-dimethylphenylcarbamate) amylose as filler, n-hexane-ethanol -Methanol-trifluoroacetic acid-diethylamine (volume ratio=70:25:5:0.2:0.1) as mobile phase; flow rate is 1ml / min; column temperature is 40°C; detection wavelength is 240nm; injection volume is 20μL .

[0050] Take the control solution and the test solution and inject them into the liquid chromatograph, respectively, and obtain the attached image 3 and attached Figure 4 chromatogram shown. S,R isomer, R,R is...

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Abstract

The invention discloses a method for simultaneous detection of contents of three isomers in palonosetron hydrochloride. The method includes following steps: (1) preparation of a mobile phase: mixing n-hexane with alcohol according to a volume ratio of (60-80):(40-20), adding a certain amount of trifluoroacetic acid and diethylamine, and obtaining the mobile phase; (2) preparation of a test solution: weighing the palonosetron hydrochloride, and preparing a solution with the concentration of 0.1-10 mg / ml through solvents; and (3) detection: detecting a sample by employing a high-efficiency liquid chromatography ultraviolet detector, wherein the ultraviolet detection wavelength is 230-250 nm, and a chromatographic column is a chiral column regarding amylose tris(3,5-dimethylphenylcarbamate) as a filling agent. According to the detection method, the operation is simple, the separation of major peaks and the isomers is good, the reservation is moderate, the sensitivity is high, it is verified that the accuracy and the precision of the analysis method are high, the specificity and the reproducibility of the method are good, and standardized operation is facilitated.

Description

technical field [0001] The invention relates to a high-sensitivity method for simultaneously detecting the content of three isomers in palonosetron hydrochloride, and belongs to the field of analysis of pharmaceutical raw materials. Background technique [0002] Palonosetron hydrochloride, chemical name: (3aS)-2-(3S)-1-azabicyclo[2,2,2]oct-3-yl-2,3,3a,4,5,6 - Hexahydro-1-benzene[trans]isoquinolin-1-one hydrochloride. This injection was developed by Helsinn Healthcare SA in Switzerland. It is a second-generation 5-HT3 receptor antagonist. Palonosetron hydrochloride was approved by the FDA in July 2003, and has been listed in a few developed countries such as the United States and Japan. . Palonosetron hydrochloride molecule contains 2 chiral centers, so there are 4 stereoconfigurations, as shown below. The two chiral centers of the active ingredient (i.e. palonosetron hydrochloride) are respectively S, S-configuration, one enantiomer configuration is R, R-configuration; th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N30/74
CPCG01N30/02G01N30/74
Inventor 王元宋君唐文生
Owner 药源生物科技(启东)有限公司
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