New sampling Strategies Committee

New sampling strategies in therapeutic drug monitoring

NEW : Update of a review on new TDM assays, described in literature, based on dried blood spot methods.  We have published a review article about TDM assays based on the dried blood spot method (DBS), earlier in June 2009 [Ther Drug Monit 2009;31:327-3361]. Now we present an update of  TDM assays based on DBS methods, which have been recently published We have published a review article about TDM assays based on the dried blood spot method (DBS), earlier in June 2009 [1]. Now we present an update of  TDM assays based on DBS methods, which have been recently published.

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’ , transdermal reverse iontophoresis. More extensive information about these techniques is given below.

Therefore the IATDMCT executive committee has founded in 2007 a scientific committee for this subject:  ‘’New Sampling Strategies’’.

Scientific committee

The aims of the committee are:

1. making up an inventory of available methods,
2. evaluation,  stimulation and coordination of  new sampling strategies in TDM.
3. information to the IATDMCT members of  new sampling strategies in TDM
4. development of guidelines

Members of the committee:

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.

• Chair: Dr L Stolk, Maastricht, The Netherlands
  lml.stolk@mumc.nl orlmlstolk@hotmail.com
• Vice-Chair: Dr P Edelbroek, Heemstede, The Netherlands
  pedelbroek@sein.nl

  Members:

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.

Recently three members of our committee published a review article about dried blood spot methods in therapeutic drug monitoring [1]. In this article the various aspects, methods and pitfalls of dried blood spot sampling are outlined. Also assays for therapeutic drug monitoring, already published in literature (52 references), based on dried blood spot methods,  are reviewed. The article is on line available for IATDMCT members on the IATDMCT website www.iatdmct.org. and for subscribers of Therapeutic Drug Monitoring at www.drug-monitoring.com.

[1] Edelbroek P, van der Heijden J, Stolk L. Dried Blood Spot Methods in Therapeutic Drug Monitoring: Methods, Assays, and Pitfalls. Ther Drug Monitor 2009, 31:327-36.

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’’. pdf1
• B Ooms,  ‘’Finger prick TDM using on-line coupling of blood sample carriers to LC-MS/MS’’. pdf2
• L Stolk, ‘’Review of Therapeutic drug monitoring with the dried blood spot method’’. pdf3
• P Edelbroek, ‘’DBS sampling in clinical epileptic practice and research’’ pdf4

Fingerprick sampling.
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.

References:
-Keevil G, Tierney D, Cooper D, Morris M, Machaal A, Yonan N. Simultaneous and rapid analysis of cyclosporine A and creatinine in finger prick blood samples using liquid chromatography tandem mass spectrometry and its application in C2 monitoring. Ther Drug Monitor.2002;24:757-767

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.

References:

-Leboulanger B, Guy RH, Delgado-Charro MB. Reverse iontophoresis for non-invasive transdermal monitoring [review]. Phsiol Meas. 2004;25:R35-50

-Leboulanger B, Aubry J, Bondolfi G, Guy R, Delgado-Charro B.Lithium monitoring  by reverse iontophoresis in vivo.Clin Chem 2004;50:2091-2100.

PDF file of a presentation in the workshop during the 2009 Montreal congress:

-M Begona Delgado-Charro  Transdermal reverse iontophoresis in TDM pdf5

• Workshop : ‘’Dried blood spot in therapeutic drug monitoring’’. IATDMC congress Nice 2007.
• Information in  IATDMCT Compass: march 2008 and September 2009.
• 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.
• We have held an enquiry by e-mail among our members about the new sampling techniques December 2008. pdf6
• A workshop and round table during the 2009 IATMCT congress in Montreal.
• Guidelines/recommendations have been developed during the business meeting of our committee during the 2009 congress.

Recommendations from the new sampling strategies committee in Montreal 2009:

• Concentrations of drugs measures after dried blood spot sampling should be reported  in the same way as is usual in conventional sampling. This means for most drugs mg/l in plasma or serum and for immunosuppressive drugs mg/l in blood.
• There should be adequate instructions and training for dried blood spot sampling by patients themselves.
• Quality control of the sampling paper used in dried blood spot sampling is of essential interest.
• Proficiency programs for new sampling methods like dried blood spot sampling should become available.
• There is need for development of devices for application in reversed iontophoresis.