Method for detecting tofacitinib chiral intermediates and enantiomer thereof

A technology of chiral intermediates and enantiomers, which is applied in the field of analytical chemistry, can solve problems such as the lack of methods for detecting optical isomers and the inability to effectively separate compounds, and achieve stable and reliable results, high sensitivity and resolution , good repeatability and durability

Active Publication Date: 2021-04-23
SHANGHAI SCIENPHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0011] CN103896946B, page 8, paragraph 0085-0087, mentions the compound N-[(3R,4R)-1-benzyl-4-methyl-3-piperidine]-N-methyl-7H-pyrrolo[2, 3-d]pyrimidin-4-amine was identified by LC-MS, but no method for detecting its optical isomers was given
[0012] Zhi, Shuang et al. [Journal of Heterocyclic Chemistry, 2016, vol.53, #4, p

Method used

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  • Method for detecting tofacitinib chiral intermediates and enantiomer thereof
  • Method for detecting tofacitinib chiral intermediates and enantiomer thereof
  • Method for detecting tofacitinib chiral intermediates and enantiomer thereof

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] 1 Chromatographic conditions:

[0042] Chromatographic column: CHIRALPAK AD-H (250mm×4.6mm, 5μm)

[0043] Detection wavelength: 277nm

[0044] Column temperature: 30°C

[0045] Flow rate: 1ml / min

[0046] Injection volume: 20μl

[0047] Diluent: mobile phase

[0048] Mobile phase: n-hexane-isopropanol-methanol-diethylamine-trifluoroacetic acid (70:20:10:0.1:0.1)

[0049] Chromatogram acquisition time: isocratic elution at least 40min

[0050] 2 Methods and results

[0051] 2.1 Solution preparation

[0052] Preparation of the test solution: take an appropriate amount of tofacitinib citrate chiral intermediate Ⅰ sample, dilute with a diluent to make 1ml of a solution containing about 0.5 mg, as the test solution.

[0053] Control solution preparation: Accurately take 1ml of the test solution and place it in a 100ml measuring bottle, add diluent to dilute to the mark, shake well, and obtain the control solution.

[0054] 2.2 System suitability

[0055] Take tofacit...

Embodiment 2

[0065] 1 Chromatographic conditions:

[0066] Chromatographic column: Kromasil 5-Amycat (250mm×4.6mm, 5μm)

[0067] Detection wavelength: 287nm

[0068] Column temperature: 30°C

[0069] Flow rate: 0.8ml / min

[0070] Injection volume: 20μl

[0071] Diluent: mobile phase

[0072] Mobile phase: n-hexane-isopropanol-methanol-diethylamine-trifluoroacetic acid (70:20:10:0.1:0.1)

[0073] Chromatogram acquisition time: isocratic elution at least 40min

[0074] 2 Methods and results

[0075] 2.1 Solution preparation

[0076] Preparation of the test solution: an appropriate amount of tofacitinib citrate chiral intermediate II sample was diluted with a diluent to make a solution containing about 0.5 mg in 1 ml as the test solution.

[0077] Control solution preparation: Accurately take 1ml of the test solution and place it in a 100ml measuring bottle, add diluent to dilute to the mark, shake well, and obtain the control solution.

[0078] 2.2 System suitability

[0079] Tofac...

Embodiment 3

[0089] 1 chromatographic column: Kromasil 5-Amycat (250mm * 4.6mm, 5 μm) replaces CHIRALPAKAD-H (250mm * 4.6mm, 5 μm) in embodiment one, all the other are the same as embodiment one,

[0090] 2 conclusions:

[0091] Under the chromatographic conditions, the chiral intermediate I of tofacitinib citrate and its enantiomers can be completely separated. Research standard technical requirements.

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Abstract

The invention belongs to the field of analytical chemistry, and particularly relates to a citric acid tofacitinib citrate chiral intermediate and an enantiomer thereof. A chromatographic column taking amylase tri(3,5-dimethyl phenyl carbamate) coated porous silica gel microspheres as a filler is adopted. A mixed solution of n-hexane-isopropanol-methanol-diethylamine- trifluoroacetic acid is used as a mobile phase for isocratic elution, and the solution enters a detector for detection. The citric acid tofacitinib citrate chiral intermediate and the enantiomer thereof can be effectively separated, and the method has the advantages of high sensitivity and separation degree, good repeatability and durability, simplicity in operation, and stable and reliable result. The method has extremely important significance in realizing the citric acid tofacitinib citrate chiral intermediate and tofacitinib citrate quality control.

Description

technical field [0001] The invention belongs to the field of analytical chemistry, and in particular relates to a method for detecting a chiral intermediate of tofacitinib and its enantiomer. Background technique [0002] Tofacitinib citrate is an oral anti-rheumatoid arthritis inhibitor developed by Pfizer (Pfrizer), the main mechanism is JAK-1 and -3 tyrosine kinase inhibitors, its chemical name is 3- ((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropane Nitrile citrate (1:1), the English name is Tofacitinib Citrate, tofacitinib citrate was approved by the US Food and Drug Administration (FDA) on November 6, 2012, and it was launched in March 2013 On the 25th, it was approved for marketing by the Japan Pharmaceuticals and Medical Devices Agency (PMDA), and on March 22, 2017, it was approved by the European Medicines Quality Agency (EDQM). [0003] The molecule of tofacitinib citrate contains 2 chiral carbon atoms, and there are fo...

Claims

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Application Information

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IPC IPC(8): G01N30/02G01N30/30G01N30/32G01N30/34G01N30/60G01N30/74
CPCG01N30/02G01N30/30G01N30/32G01N30/34G01N30/60G01N30/74G01N2030/324
Inventor 姜春阳李惠谢军王倩周小群许全胜
Owner SHANGHAI SCIENPHARM CO LTD
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