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Dear all,
We are looking for a laboratory to analyze PK samples for eflornithine
(-difluoromethylornithine or DFMO) and nifurtimox (3-Methyl-4-[(5-
nitrofurfurylidene)amino]thiomorpholine 1,1-dioxide; 3-methyl-N-[(5-
nitro-2-furanyl)methylene]-4-thiomorpholinamine 1,1-dioxide; or
Lampit) of a future study concerning sleeping sickness (human African
trypanosomiasis).
Whereas we are of the opinion the analysis of nifurtimox should not be
very problematic, the published methods for eflornithine are quite
cumbersome (pre- or post-column derivatization).
Does anybody have knowledge of a) more modern methods and/or b) on
laboratories (academic or commercial) which would be able to conduct
such a quantitative analysis?
References:
Eflornithine:
Hanpitakpong W. et al; J Chromatogr B Analyt Technol Biomed Life Sci.
2003 May 25;788(2):221-31.
Kilkenny ML et al.; J Pharm Biomed Anal. 1998 Sep 1;17(6-7):1205-13.
Huebert ND et al; J Chromatogr A. 1997 Feb 21;762(1-2):293-8.
Loiseau PM et al ; Parasitol Res. 1997;83(4):386-9.
Hu T et al; J Chromatogr A. 1995 Nov 17;716(1-2):381-8.
Cohen JL et al; J Pharm Sci. 1989 Feb;78(2):114-6.
Smithers J.; Pharm Res. 1988 Oct; 5(10): 684-686.
Nifurtimox:
1.) Paulos C et al., J Chromatogr. 1988 Dec 9;433:359-62,
2.) Medenwald H et al.; Arzneimittelforschung. 1972 Sep;22(9):
1613-7.
Best regards,
--
Sonja Bernhard, PhD
Clinical Research Associate
Pharmaceutical Medicine Unit
Swiss Tropical Institute
Socinstrasse 57
P.O. Box
CH-4002 Basel
Switzerland
www.sti.ch
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The following message was posted to: PharmPK
Dear Sonja,
The structure of the first compound looks particularly suited to HILIC
or hydrophylic interaction chromatography, coupled with MS. In all
likelihood, the other compound, though not a small hydrophilic entity
(for which HILIC is typically employed), will still chromatograph OK
as well. As with most LC-MS assays, good internal standards will be
key (either stable isotope, or an extra carbon).
Good luck, Jan
--
Jan Hendrik Beumer
Pharm.D., Ph.D.
Assistant Professor of Pharmaceutical Sciences
School of Pharmacy
The Hillman Cancer Center
Research Pavilion, Suite G.27d
5117 Centre Avenue
Pittsburgh, PA 15213-1863
Email: beumerjh.at.upmc.edu
http://www.pharmacy.pitt.edu/Directory/dir.lasso?Last=BeumerJ
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The following message was posted to: PharmPK
Hi Sonja.
Nifurtimox can be measured by relatively simple HPLC.
We have setup the method for a clinical study in Chagas, so I can put
you in contact with the people in the lab (in Argentina) to see if we
can be of any help.
Eflornithine is probably a different story, but as Dr Beumer mentions,
it should not be that difficult with LC-MS.
Malm and Bergqvist developed a method for Eflornithine that does not
require derivatization, but you need an evaporative light scattering
detector (Malm M, Bergqvist Y. Determination of eflornithine
enantiomers in plasma, by solid-phase extraction and liquid
chromatography with evaporative light-scattering detection. J
Chromatogr B Analyt Technol Biomed Life Sci. 2007 Feb 1;846(1-2):
98-104. Epub 2006 Sep 22.)
Have you tried contacting Sanofi-Aventis? The online EMEA scientific
discussion on the approval of Vaniqa (eflornithine cream to treat
hirsutism...) mentions that the drug was measured with LC-MS-MS in
blood of volunteers.
http://www.emea.europa.eu/humandocs/PDFs/EPAR/vaniqa/021201en6.pdf
page 4
Please let me know if there is anything I can do to help,
Yours,
Facundo Garcia-Bournissen, MD
Division of Clinical Pharmacology & Toxicology,
Hospital for Sick Children, University of Toronto,
Toronto, ON Canada
email: facundo.garciabournissen.aaa.sickkids.ca
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