Novel, heavy vitamin B12 derivatives
The invention discussed in this application relates to vitamin B12-based compounds that are useful as quantitative standards, particularly for the assessment of vitamin B12 deficiency.
1. A method of assessing a patient for vitamin B12 deficiency, the method comprising:
administering to a patient an effective amount of a heavy vitamin B12 having a mass shift of at least +7 over unlabeled vitamin B12,
obtaining a biological fluid sample from the patient, and
analysing the sample to determine the quantity of the heavy vitamin B12 in the sample,
wherein the heavy vitamin B12 includes seven 13 C atoms and the seven 13 C atoms are located in the dimethylbenzimidazole moiety of the vitamin.
2. The method of claim 1 , wherein the biological fluid sample is a blood sample.
3. The method of claim 2 , wherein the red blood cells are separated from the serum.
4. The method of claim 1 , wherein the heavy vitamin B12 is administered orally or parenterally.
5. The method of claim 1 , wherein the heavy vitamin B12 is in an aqueous solution.
6. The method of claim 1 , wherein the patient consumes a small meal following administration of the heavy vitamin B12.
7. The method of claim 6 , wherein the meal is a low fat breakfast.
8. The method of claim 1 , wherein the patient is administered about 1.5 micrograms heavy vitamin B12.
9. The method of claim 1 , wherein the analysis indicates whether the patient has a vitamin B12 deficiency or suffers from vitamin B12 malabsorption.
10. The method of claim 1 , wherein the patient is a primate, domesticated companion animal or livestock.
11. The method of claim 10 , wherein the patient is human.
12. The method of claim 1 , wherein the analysis is conducted using high performance liquid chromatography followed by mass spectrometry.
13. The method of claim 1 , wherein the biological fluid sample is separated into three equal-volume subsamples: subsample 1, subsample 2 and subsample 3.
14. The method of claim 13 , wherein an amount of 13 C 7 -cyanocobalamin is added to one or more of subsample 1, subsample 2, and subsample 3.
15. The method of claim 1 , wherein the heavy vitamin B12 has a mass shift of from +7 to +10 over unlabeled vitamin B12.
16. The method of claim 1 , wherein the heavy vitamin B12 is a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, solvate or prodrug thereof:
wherein
R is selected from 5′-deoxyadenosyl, OH, H 2 O, CH 3 , or CN.
17. The method of claim 1 , wherein the seven 13 C atoms are located in the dimethylbenzimidazole moiety as follows:
18. The method of claim 1 , wherein 13 C-labeled dimethylbenzimidazole moiety has one or more 2 H atoms.
19. The method of claim 18 , wherein the one or more 2 H atoms are also located in the dimethylbenzimidazole moiety of the vitamin.
20. The method of claim 1 , wherein the heavy vitamin B12 is heavy cyanocobalamin, heavy hydroxocobalamin, heavy deoxyadenosylcobalamin, heavy methylcobalamin or combinations thereof.