Solid phase conditioning

Patent metadata

Field	Value
Publication number	US-2020047158-A1
Application number	US-201716472747-A
Country	US
Kind code	A1
Filing date	Dec 21, 2017
Priority date	Dec 21, 2016
Publication date	Feb 13, 2020
Grant date	—

Abstract

The present invention relates to a method for conditioning reversed phase SPE cartridges that provides certain advantages compared with known such methods. The method of the invention finds particular use in the automated synthesis of radiolabeled compounds where SPE is used for example in the purification steps.

First claim

1 . A method to condition a reversed phase solid phase extraction (SPE) cartridge wherein said method comprises the sequential steps of passing:
(i) an inorganic solvent wherein said inorganic solvent is acidic or alkaline; (ii) a polar organic solvent; and, (iii) a low-strength solvent; through said SPE cartridge.

2 . The method as defined in claim 1 wherein said reversed phase SPE cartridge is a tC18 SPE cartridge.

3 .- 8 . (canceled)

9 . The method as defined in claim 1 wherein said polar organic solvent is selected from tetrahydriofuran (THF), dichloromethane (DCM), dimethylformamide (DMF), acetonitrile (MeCN), dimethyl sulfoxide (DMSO), acetic acid, t-butanol, n-propanol, ethanol (EtOH) or methanol (MeOH).

10 . (canceled)

11 . The method as defined in claim 1 wherein said low-strength solvent is selected from water or a buffer.

12 .- 14 . (canceled)

15 . The method as defined in claim 1 wherein said inorganic solvent is acidic.

16 . The method as defined in claim 15 wherein said inorganic solvent is selected from HCl, H 3 PO 4 or H 2 SO 4 .

17 . The method as defined in claim 1 wherein said inorganic solvent is alkaline.

18 . The method as defined in claim 17 wherein said inorganic solvent is selected from KOH, NaOH, K 2 CO 3 or a tetraalkylammonium salt.

19 . The method as defined in claim 1 wherein said conditioning further comprises the following step (iv) of passing a low-strength solvent through said SPE cartridge wherein said low-strength solvent is selected from water or a buffer.

20 . The method as defined in claim 1 wherein between 0.2-2.0 mL of said inorganic solvent is passed through said SPE cartridge in said conditioning step.

21 . (canceled)

22 . A conditioned reversed phase SPE cartridge obtainable by the method as defined in claim 1 .

23 . Use of the conditioned reversed phase SPE cartridge as defined in claim 22 in the manufacture of a radiopharmaceutical.

24 . The use as defined in claim 23 wherein said radiopharmaceutical comprises a single-photon emission tomography (SPECT) tracer or a positron-emission tomography (PET) tracer.

25 .- 26 . (canceled)

27 . A method for the production of a radiolabelled compound comprising:
(a) reacting a precursor compound with a suitable radioisotope to obtain a reaction mixture; (b) processing said reaction mixture on one or more conditioned reversed phase SPE cartridges, wherein each of said conditioned reversed phase SPE cartridges is as defined in claim 22 .

28 . The method as defined in claim 27 wherein said precursor compound comprises protecting groups, said reaction mixture comprises a protected radiolabelled intermediate, and said processing comprises removal of said protecting groups.

29 . The method as defined in claim 28 wherein removal of said protecting groups is carried out by passing the reaction mixture through said SPE cartridge to trap said protected radiolabelled intermediate and then passing a deprotecting reagent through said SPE cartridge to obtain said radiolabelled compound.

30 . The method as defined in claim 1 wherein said processing comprises purification of said reaction mixture to obtain said radiolabelled compound in a purified form.

31 . The method as defined in claim 1 wherein said radiolabelled compound is a single-photon emission tomography (SPECT) tracer or a positron-emission tomography (PET) tracer.

32 .- 36 . (canceled)

37 . A method to deprotect a protected radiolabelled intermediate wherein said method comprises trapping said protected radiolabelled intermediate onto a conditioned reversed phase SPE cartridge as defined in claim 22 and then passing a deprotecting reagent through said SPE cartridge to obtain a deprotected radiolabelled compound.

38 . A method to purify a reaction mixture comprising a radiolabelled compound wherein said method comprises passing said reaction mixture through a conditioned reversed phase SPE cartridge as defined in claim 22 .

Assignees

• Ge Healthcare Ltd

Inventors

• Verbrugge Nicolas
• Franci Xavier Y A
• Thawinwisan Natthawadee

Classifications

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title

• C07B59/00

  Introduction of isotopes of elements into organic compounds {; Labelled organic compounds per se} · CPC title

• B01J2220/62

  In a cartridge · CPC title

• B01D15/325

  Reversed phase · CPC title

• B01D15/203

  Equilibration or regeneration · CPC title