Determination method for content of tofacitinib citrate and related substances of tofacitinib citrate by reversed phase high-performance liquid chromatography

A reversed-phase high-efficiency liquid phase and tofacitinib technology, which is applied in the field of medicine, can solve problems affecting baseline noise and drift, pressure instability, and easy generation of bubbles, etc., to reduce the requirements of instruments, stabilize pressure, and facilitate experimental operations Effect

Active Publication Date: 2016-02-17
NINGBO LIWAH PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] 1. This method uses gradient elution; it has high requirements on the instrument, and it is easy to generate bubbles, which will affect the baseline noise and drift, and will cause pressure instability at the same time

Method used

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  • Determination method for content of tofacitinib citrate and related substances of tofacitinib citrate by reversed phase high-performance liquid chromatography
  • Determination method for content of tofacitinib citrate and related substances of tofacitinib citrate by reversed phase high-performance liquid chromatography
  • Determination method for content of tofacitinib citrate and related substances of tofacitinib citrate by reversed phase high-performance liquid chromatography

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Example 1: Determination of reversed-phase high-performance liquid chromatography of tofacitinib citrate content

[0032] Chromatographic conditions and system suitability test: use octadecylsilane bonded silica gel as filler; use 0.02mol / L potassium dihydrogen phosphate solution (containing 0.2% triethylamine, adjust the pH value to 5.2 with phosphoric acid)-acetonitrile ( 83:17) is the mobile phase; the detection wavelength is 290nm; the column temperature is 30°C. The number of theoretical plates is not less than 3000 based on the peak of tofacitinib.

[0033] Get the tofacitinib citrate test sample, accurately weighed, dissolve and quantitatively dilute with methanol-water (90:10) and make the test sample solution containing about 1mg of tofacitinib citrate in every 1ml, Precisely measure 10 μl of the sample solution to be tested and inject it into the liquid chromatograph, and record the chromatogram; another tofacitinib citrate reference substance is taken for de...

Embodiment 2

[0034] Embodiment 2: Determination of related substances of tofacitinib citrate by reversed-phase high-performance liquid chromatography:

[0035] Chromatographic conditions and system suitability test: use octadecylsilane bonded silica gel as filler; use 0.02mol / L potassium dihydrogen phosphate solution (containing 0.2% triethylamine, adjust the pH value to 5.2 with phosphoric acid)-acetonitrile ( 83:17) is the mobile phase; the detection wavelength is 290nm; the column temperature is 30°C. The number of theoretical plates is not less than 3000 based on the peak of tofacitinib, and the tailing factor is less than 1.5.

[0036] Get the tofacitinib citrate test sample described in Example 1, accurately weighed, dissolve and dilute with methanol-water (90:10) and make about containing tofacitinib citrate 5mg in every 1ml solution, as the test solution. Accurately measure an appropriate amount of the test solution, dilute with methanol-water (90:10) to make a solution containin...

Embodiment 3

[0047] Embodiment 3 verifies the following items of assay

[0048] a) Instrument precision test

[0049]Take about 20mg of tofacitinib citrate, accurately weigh it, put it in a 20ml volumetric flask, add methanol-water (90:10) to the near scale, ultrasonically treat it, take it out, let it cool to room temperature, add methanol-water (90:10 :10) to scale, shake up, filter, get the continued filtrate, as need testing solution. Precisely measure 10 μl of the test solution, inject it into the liquid chromatograph, record the chromatogram, repeat the injection 6 times, and calculate the RSD value of the peak area. The results are shown in Table 2 below.

[0050] Table 2 Results of precision test of content determination instrument

[0051]

[0052] Conclusion: The RSD is 0.07%, indicating that the precision of the instrument is good.

[0053] b) Recovery rate test

[0054] Take tofacitinib citrate working reference substance 15.80, 15.77, 15.85, 19.76, 19.90, 20.45, 23.96,...

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Abstract

The invention discloses a determination method for the content of tofacitinib citrate and related substances of the tofacitinib citrate by reversed phase high-performance liquid chromatography. The determination method is characterized in that octadecylsilane chemically bonded silica is taken as filler; 0.02mol / L potassium dihydrogen phosphate solution and acetonitrile with volume ratio of 83:1 are taken as a mobile phase to perform isocratic elution, and the flow speed is 1.0ml / min; the 0.02mol / L potassium dihydrogen phosphate solution contains trimethylamine with mass concentration of 0.2 percent, and pH value is adjusted to 5.2 by using phosphoric acid; the detection wavelength is 290nm, and the column temperature is 30DEG C. According to the determination method disclosed by the invention, by adopting the isocratic elution, requirements on an instrument are reduced, as well as stable pressure and accurate and reliable experimental result are obtained; meanwhile, by adopting the method disclosed by the invention, the concentration of linear range is improved, and the preparation for a test solution during experiment is facilitated.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a method for determining the content of tofacitinib citrate and its related substances by reversed-phase high-performance liquid chromatography. Background technique [0002] Tofacitinib citrate is a new drug jointly developed by Takeda Pharmaceutical Co., Ltd. of Japan and Pfizer of the United States for patients with moderately to severely active rheumatoid arthritis who have insufficient response or intolerance to methotrexate treatment. The drug for adult patients with arthritis (RA) was approved by the US FDA on November 6, 2012, and the trade name is XELJANZ. [0003] Its structure is as follows: [0004] [0005] Chemical name: 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)- 3-oxopropionitrile citrate (1:1). [0006] Tofacitinib is white to off-white crystalline powder, easily soluble in dimethyl sulfoxide, slightly soluble in 0.1mol / L hyd...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02
Inventor 孙卓亚胡艳嫔张旭徐旭峰王腾峰陈斌吕波
Owner NINGBO LIWAH PHARM CO LTD
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