Method for detecting trifluridine-related substance by high-performance liquid chromatography

Patent metadata

Field	Value
Publication number	US-10809237-B2
Application number	US-201916442993-A
Country	US
Kind code	B2
Filing date	Jun 17, 2019
Priority date	Jan 5, 2018
Publication date	Oct 20, 2020
Grant date	Oct 20, 2020

Abstract

The present invention provides a novel method that is capable of detecting a trifluridine-related substance from a sample containing trifluridine or a salt thereof by high-performance liquid chromatography comprising two steps that are performed under gradient conditions. More specifically, the method is for detecting a trifluridine-related substance, the method comprising the step of subjecting a sample containing trifluridine or a salt thereof to high-performance liquid chromatography using a mobile phase composed of an organic phase and an aqueous phase, wherein the step of high-performance liquid chromatography comprises steps 1 and 2 that satisfy the following requirements: Step 1: the percentage of the organic phase in the entire mobile phase is 1 to 14% by volume; and Step 2: after step 1, elution is performed by applying a gradient of increasing the percentage of the organic phase in the entire mobile phase.

First claim

The invention claimed is:

1. A method for detection, comprising:
subjecting a sample including trifluridine or a salt thereof to high-performance liquid chromatography with a mobile phase comprising an organic phase and an aqueous phase, and
detecting 5′-(4-chlorophenylcarboxy)-2′-deoxy-5-trifluoromethyluridine in the sample by the high-performance liquid chromatography,
wherein the high-performance liquid chromatography comprises steps 1 and 2, step 1 is conducted with the mobile phase including the organic phase in a range of from 1 to 14% by volume, step 2 is conducted after step 1 and includes performing elution by applying a gradient of increasing the percentage of the organic phase in the mobile phase,
the organic phase comprises at least one solvent and optionally 10% or less water,
the aqueous phase comprises water and optionally 10% or less of at least one solvent, and
the 5′-(4-chlorophenylcarboxy)-2′-deoxy-5-trifluoromethyluridine is detected in the mobile phase of step 2.

2. The method according to claim 1 , wherein step 1 is performed under isocratic conditions.

3. The method according to claim 1 , wherein the organic phase is acetonitrile.

4. The method according to claim 1 , wherein, in step 1, the percentage of the organic phase in the mobile phase is within a range of 2 to 10% by volume.

5. The method according to claim 1 , wherein the percentage of the organic phase in the mobile phase at the end of step 2 is within a range of 25 to 70% by volume.

6. The method according to claim 1 , wherein, in step 2, the elution is performed by applying a gradient of increasing the percentage of the organic phase in the mobile phase by 0.9% by volume or more per 1 minute.

7. The method according to claim 1 , wherein step 2 has a measurement time within a range of 10 to 50 minutes.

8. The method according to claim 1 , wherein a flow rate at the end of step 2 is 1.0 to 1.5 times a flow rate in step 1.

9. The method according to claim 1 , wherein the aqueous phase includes phosphate.

10. The method according to claim 1 , wherein the aqueous phase includes methanol.

11. The method according to claim 1 , wherein, in step 1, the percentage of the organic phase in the mobile phase is within a range of 3 to 7% by volume.

12. The method according to claim 1 , wherein, in step 2, the elution is performed by applying a gradient of increasing the percentage of the organic phase in the mobile phase by 1.0% by volume or more per 1 minute.

13. The method according to claim 1 , wherein, in step 2, the elution is performed by applying a gradient of increasing the percentage of the organic phase in the mobile phase by 2.0% by volume or more per 1 minute.

14. The method according to claim 1 , wherein, in step 2, the elution is performed by applying a gradient of increasing the percentage of the organic phase in the mobile phase by 2.0% by volume or more and 5.0% by volume or less per 1 minute.

15. The method according to claim 2 , wherein the percentage of the organic phase in the mobile phase at the end of step 2 is within a range of 30 to 65% by volume.

16. The method according to claim 1 , wherein the percentage of the organic phase in the mobile phase at the end of step 2 is within a range of 35 to 60% by volume.

17. A quality control method of a combination drug including trifluridine, comprising:
performing the method of claim 1 ,
wherein the sample is the combination drug.

18. A method of detecting impurities in a combination drug including trifluridine, comprising:
performing the method of claim 1 ,
wherein the sample is the combination drug.

Assignees

• Taiho Pharmaceutical Co Ltd

Inventors

• Takeda Daisuke
• Kojima Akiyo

Classifications

• G01N30/34 Primary

  of fluid composition, e.g. gradient (G01N30/36 takes precedence) · CPC title

• C07D239/54

  as doubly bound oxygen atoms or as unsubstituted hydroxy radicals · CPC title

• G01N2030/884

  organic compounds · CPC title

• G01N2030/8845

  involving halogenated organic compounds · CPC title

• G01N30/36 Primary

  in high pressure liquid systems · CPC title