New sampling Strategies Committee
New Sampling Strategies Committee
New sampling strategies in therapeutic drug monitoring
Last update: December 2011
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’ , transdermal reverse iontophoresis. More extensive information about these techniques is given below.
The IATDMCT Executive Committee has founded in 2007 a scientific committee for this subject: ‘’New Sampling Strategies’’.
The aims of the Committee are:
- making up an inventory of available methods
- evaluation, stimulation and coordination of new sampling strategies in TDM
- information to the IATDMCT members of new sampling strategies in TDM
- development of guidelines
Members of the Committee:
• Vice-Chair: Dr JW Alffenaar , Groningen, The Netherlands
|Dr. Y. Berqvist||Stockholm, Sweden|
|Dr. M. Begona |
|Bath, United Kingdom|
|Dr. M. Boettcher||Dessau-Rosslau, Germany|
|Dr. P. Edelbroek||Leiden, The Netherlands|
|M. Green||Whatman International, Maidstone, United Kingdom|
|Dr. P. Hooper||New Orleans, USA|
|Dr. B. Keevil||Manchester, UK|
|Dr. R. Linden||Rio de Janeiro, Brazil|
|Dr. J. Millership||Belfast, Northern Ireland|
|B. Ooms||Emmen, The Netherlands|
|Dr. C. Stove||Gent, Belgium|
|TECHNIQUES OF NEW SAMPLING STRATEGIES|
|The dried blood spot method (DBS)|
|The patient makes a fingerprick himself 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 many classes of drugs: immunosuppressive drugs, antiretroviral drugs, antimalarials, antiepileptic drugs, antibiotics 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.|
Review article about dried blood spot.
|IATDMCT website www.iatdmct.org|
|and for subscribers of Therapeutic Drug Monitoring at www.drug-monitoring.com.|
|Update review article. |
A 2010 update of above review on new TDM assays based on dried blood spot method, has been written by L Stolk.
|Many publications about the dried blood spot can be found in:|
|The journal of pharmaceutical en biomedical analysis |
|Overview of DBS Applications For Drugs Of Abuse|
|by By Christophe Stove, Ann-Sofie Ingels, Pieter De Kesel, Nele Sadones & Willy Lambert, Laboratory of Toxicology, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University|
|Pdf files of the presentations about the dried blood spot method presented in the workshop of the committee during the 2009 Montreal congress:|
|J Millership |
The use of dried blood spot sampling for the determination of drugs in children and neonates
|B Ooms |
Finger prick TDM using on-line coupling of blood sample carriers to LC-MS/MS
| L Stolk |
Review of Therapeutic drug monitoring with the dried blood spot method.
|P Edelbroek |
DBS sampling in clinical epileptic practice and research
|Pdf files of the presentations about the dried blood spot method presented in the workshop of the committee during the 2011 Stuttgart congress:|
|Dr C Stove. |
DBS in Toxicology: On spot derivatisation and GC-MS determination in dried blood spots
|B Ooms. |
New developments in DBS: On line DBS analysis.
|Dr Jeff Millership. |
DBS with children and neonates.
|Prof Dr Yngve Bergqvist. |
DBS with antimalarials in third world countries.
|Dr L Stolk. |
Some new developments and insights with the dried blood spot method.
|Fingerprick sampling by the patients 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.|
-Keevil B, Fides J, Baynes A et al. Liquid chromatography-mass spectrometry measurement of tacrolimus in finger-prick samples compared with venous whole blood samples. Ann Clin Biochem 2009;46:144-5
|Transdermal reverse iontophoresis|
Initially developed for transdermal drug delivery, iontophoresis has also been investigated as an alternative, non-invasive samping technique. The potential application of this technique for monitoring drugs has been reviewed recently. Two mechanisms of transport are involved in iontophoresis. Electromigration involves the movement of ions, which carry charge across the skin and are driven (attracted) specifically toward the electrode of opposite polarity.
Electroosmosis is a net solvent flow in the anode to cathode direction, which enables much improved permeation of neutral species (eg glucose) and further enhances cationic transport.
Leboulanger B, Guy RH, Delgado-Charro MB. Reverse iontophoresis for non-invasive transdermal monitoring [review]. Phsiol Meas. 2004;25:R35-50
|PDF file of a presentation in the workshop during the 2009 Montreal congress:|
|M Begona Delgado-Charro |
Transdermal reverse iontophoresis in TDM
|Poster Stuttgart congress|
|ACTIVITIES OF THE COMMITTEE|
|Workshop: ‘’Dried blood spot in therapeutic drug monitoring’’. IATDMC congress Nice 2007.|
|Information in IATDMCT Compass: march 2008, september 2009, 2010 and 2011.|
|Review article about dried blood spot sampling in therapeutic drug monitoring, which gives an overview of existing assays and methods, in the journal ‘’Therapeutic Drug Monitoring’’ june 2009. Ther Drug Monit 2009;31:327-3361|
|2010 update of a review on new TDM assays, described in literature, based on dried blood spot methods.|
|We have held an enquiry by e-mail among our members about the new sampling techniques December 2008.|
|A workshop and roundtable during the 2009 IATMCT congress in Montreal.|
|Participation and presentations during the multiple international workshop in Brussels 17-18 june 2010 “Connecting strategies on dried blood spots’’. www.europeanbioanalysisforum.eu|
A workshop during the 2011 IATDMCT Congress in Stuttgart.
|Recommendations from the new sampling strategies committee:|
|Stuttgart Congress 2011|
|There was a business meeting of committee during the 2011 Stuttgart Congress. |
Minutes of this meeting: pdf13
|Future activities of the committee:|