New sampling

New sampling strategies in therapeutic drug monitoring

Introduction
Venous sampling and consecutive assay of medicines in plasma, serum or sometimes in whole blood is common practice in therapeutic drug monitoring (TDM). However some possible draw-backs can be thought of for venous sampling. Venous sampling demands an experienced phlebotomist and usually patients have to leave their home. Blood samples are bio-hazardous material and package for shipment and storage should cope with official guidelines. Limited stability of medicines in liquid blood samples during transport and storage is another problem with unstable medicines.
Therefore there exists increasing interest for alternative sampling methods in TDM. Alternative sampling methods are for example ‘dried blood spot sampling’ (DBS), ‘fingerprick sampling’ instead of venous sampling or measurement in ‘’another matrix’’ like oral fluid. More extensive information about these techniques is given below.
The IATDMCT executive committee has founded a scientific committee for this subject: ‘’New Sampling Strategies’’.
Aims of the committee are making up an inventory of available methods, development of guidelines, coordination, evaluation and stimulation of new sampling strategies in TDM.
Dr. Leo Stolk and Dr. Peter Edelbroek from the Netherlands co-chair this committee with an initial interest in the dried blood spot sampling technology.
Information: lml.stolk@mumc.nl

New sampling strategies
The dried blood spot method: The patient makes a fingerprick himselve and whole blood is applied to sampling paper. After drying and shipment, the spot or part of it is extracted and analysed in the laboratory. Recently dried blood spot technology has been proposed for TDM of various classes of drugs. Immunosuppressive drugs like ciclosporin, tacrolimus and everolimus. Antiretroviral drugs: protease inhibitors but also nucleoside reverse transciptase inhibitors. Antimalarials: piperaquine, dapsone, pyrimethamine and sulfadoxine and nearly all antiepileptic drugs. The antibiotics rifampicin, gentamicin, netilmicin and miscellaneous drugs, such as metformin, acetaminophen and theophylline. A wide range of assay techniques are used with DBS: HPLC-tandem MS, HPLC-UV and immunoassay. However there is need for standardization, quality assurance, basic research and development of more assays with the dried blood spot technology. See also abstracts of workshop no 7 IATDMCT congress Nice Sep 2007.
Fingerprick sampling. Fingerprick sampling by the patient himself and consecutive transport of capillary blood is another alternative sampling method in TDM. Devices for transport of (diluted) capillary blood samples and sorbent sampling devices are being developed.
Oral fluid in TDM. Oral fluid (or saliva) concentrations are thought to reflect the free drug plasma concentrations. Thus in clinical conditions in which protein binding varies, oral fluid drug concentration is more closely related to the therapeutically active concentration than the plasma concentration. The primary requisite for oral fluid monitoring to be useful is a constant or predictable relationship between drug concentrations in oral fluid and plasma.
Langman L. The use of oral fluid for therapeutic drug management. Ann NY Acad Sci 2007;1098:145-166.


Activities of the committee
-Workshop : ‘’Dried blood spot in therapeutic drug monitoring’’. IATDMCT congress Nice 2007.
-Introduction of the committee in IATDMCT Compass: march 2008.
-Review article about dried blood spot sampling in therapeutic drug monitoring, which gives an overview of existing assays and methods, has been submitted to the journal ‘’Therapeutic Drug Monitoring’’.
-Development of Guidelines is under discussion now.
-A workshop is planned for the 2009 IATDMCT congress in Montreal.

List of participants of the committee:

Chairs:
-Dr P Edelbroek Heemstede, The Netherlands
-Dr L Stolk Maastricht, The Netherlands

Members: