37


S. Fowles, J. Chromatogr. B 870 (2008) 32–37


9. R.J.W. Meesters, G.P. Hooff, Bioanalysis, 5 (2013) 2187–2208


10. S. Brookes, K. Woodmansey, I. Love, Chromatography Today 36 – 39, May/ June 2010


11. P. Denniff, N. Spooner, Bioanalysis, 2 (2010) 1385–1395


Figure 3 Agilent Automated Card Extraction Dried Blood Spot LC/MS (AACE DBS LC/MS) system, based on the ProLab concept


Microsampling Capillaries


There are a variety of organisations that supply capillaries that will allow the sampling of the blood as it is removed from the patient. The capillaries are designed to have a set internal diameter and also a set length, which implies that there will be a set volume. Commercially available tubes exist in volumes as small as 250 nL up to 200 µL, with many different sizes that would accommodate volumes required for bioanalysis. The use of capillary action ensures that the capillary is filled. Once filled the capillary can then be used directly or the contents can be transferred to another sampling device such as Guthrie card or similar type of adsorbent paper material.


One of the most successful approaches that has been investigated is the use of Drummond tubes for the analysis of plasma samples. Initial work by [26] investigated the use of a blood sample of 75 µL taken into an EDTA coated, microcapillary containing thixotropic gel & self-sealing plug. The method then centrifuged an inverted microcapillary in 1.4 mL Micronic tube fitted with a pre-split cap. The tube acts as convenient holder and also facilitates labelling. The separated plasma, typically having a volume of 40 – 45 µL, was subsequently dispensed into labelled screw-top tubes. Bioanalytical methods were then developed which used 15 µL of plasma sample.


Conclusion


There is a substantial drive for the pharmaceutical and clinical markets to embrace microsampling. As discussed here there are several approaches that can be employed to satisfy this driver, however as yet very few, if any, of these approaches have been used in regulatory studies. The obvious issue with the whole blood analysis is the


HCT effect and this needs to be addressed before this approach can be successfully employed within the pharmaceutical industry for regulated bioanalysis. The use of micro plasma samples does offer some distinct advantages over the whole blood approach, since it very much matches the technology that is currently used in many laboratories and consequently would be substantially easier to implement for most bioanalytical laboratories. The drivers for microsampling will be ever present and with the increase in sensitivity associated with modern mass spectrometers and the advancement of sample preparation technology, more and more emphasis will be placed on handling of the sample rather than the techniques to allow the quantification of the test compounds.


References


1. http://learnpkpd.com/2013/11/25/ understanding-steady-state- pharmacokinetics/


2. http://www.dandybooksellers.com/ acatalog/9780853695714.pdf


3. K. Chapman, S. Chivers, D. Giddon, D. Mitchell, S. Robinson, T. Sangster, S. Sparrow, N. Spooner, A. Wilson, Drug Discover Today, 19 (5) (2014) 528 – 532


4. C. Smith, A. Sykes, S. Robinson, E. Thomas, Bioanalysis, 3(2) (2011) 145-156


5. Microsampling in pharmaceutical bioanalysis, P. Zane, G.T. Emmons, pub. Future Science Group


6. S. White, G. Hawthorne, L. Dillen, N. Spooner, K. Woods, T. Sangster, Z. Cobb, P. Timmerman, Bioanalysis, 6 (19) (2014) 2581-2586


7. R. Guthrie, A. Susi, Pediatrics, Sep. 32 (1963) 338–343


8. M. Barfield, N. Spooner, R. Lad, S. Parry,


12. P.M. De Kesel, N. Sadones, S. Capiau, W.E. Lambert, C.P. Stove, Bioanalysis, 5 (2013) 2023–2041


13. J. Rudge, S. Kushon, A. Bischofberger, A. Carpenter, P. Denniff, Y. Guo, P. Rahn, N. Spooner, S. Osborne, E. Welch, C. Cordova, J. Layne, Chromatography Today 38-40, Nov. / Dec. 2014


14. R.M. Sturm, J. Henion, R. Abbott, P. Wang, Bioanalysis, 7(16) (2015) 1987-2002


15. A.J. Wilhelm, C.G. J.C.G. den Burger, E.L. Swart, Clin. Pharmacokinet., 53(11) (2014) 961–973


16. Y. Li, J. Henion, R. Abbott, P. Wang, Rapid Commun. Mass Spectrom., 26 (2012) 1208–1212


17. J.H. Kim, T. Woenker, J. Adamec, F.E. Regnier, Anal. Chem., 85 (2013) 11501– 11508


18. N. Ganz, M. Singrasa, L. Nicolas, M. Gutierrez, J. Dingemanse, W. Döbelin, M. Glinski, J. Chromotogr. B. 885-886 (2012) 50-60


19. A.A. Alfazil, R.A. Anderson, J. Anal. Toxicol. 32 (2008) 511–515


20. R.V. Oliveira, J. Henion, E. Wickremsinhe, Anal. Chem., 86 (2), (2014) 1246–1253


21. J.A. Ooms, L. Knegt, E. Hermannus, M. Koster, Bioanalysis, 3(20) (2011) 2311-2320


22. R.V. Oliveira, J. Henion, E.R. Wickremsinhe, Bioanalysis, 6(15) (2014) 2027-2041


23. C-H. Lin, W-C. Liao, C. Hsin-Kai, T-Y. Kuo, Bioanalysis 6(2) (2014) 199–208


24. Q. Yang, H. Wang, J.D. Maas, W.J. Chappell, N.E. Manicke, R.G. Cooks, Z. Ouyang, Int. J. Mass Spectrom., 312 (2012) 201–207


25. J. Liu, H. Wang, N.E. Manicke, J.M. Lin, Z. Ouyang, R.G. Cooks, Anal. Chem. 82(6) (2010) 2463–2471


26. C.L. Bowen, H. Licea-Perez, M.Z. Karlinsey, K. Jurusik, E. Pierre, J. Siple, J. Kenney, A. Stokes, N. Spooner, C.A. Evans, Bioanalysis, May, 5(9) (2013) 1131-5


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60