drugs in plasma and serum

[just me]

hello
On looking through papers i notice that quite a lot of drugs are measured from plasma and serum . Why do we not measure drug levels in blood ? Surely this is more appropriate than looking at plasma and serum levels ?

[chromatographer1]

The red blood cells can be quite difficult to work with in trying to measure drug content. That is why they are separated out and just the serum tested for drugs. Historically, it seems that toxicologists have found that accurate numbers can be determined using serum only instead of whole blood.

[just me]

not meaning to be difficult but what do u mean by difficult to work with ???

[tom jupille]

They are separate cells, so you have to be able to get at the contents. This means, at a minimum, lysing (or otherwise disrupting) the cells, then getting rid of the resulting debris.

[HW Mueller]

just me,
if you think it´s more appropriate to use whole blood than the next guy can say it´s more appropriate to mince the whole being. You have to start somewhere, plasma/serum is easy to get. Many people go even the other direction, they subdivide plasma/serum (for instance looking at proteins and aqu. part separatly if one wants to know whether a substance adheres to albumin) or need plasma rather than serum (if one looks at fibrin, as an example). Remember, the none-cell portians of blood are responsible for the transport of most substances. If you were interested in oxygen transport you would presumably look at the erythrocytes......

[tom jupille]

just me,
if you think it´s more appropriate to use whole blood than the next guy can say it´s more appropriate to mince the whole being.

Wow, that's a scary thought! Then reprocess the leftovers as "Soylent Green"?

[HW Mueller]

How did we get into this? . . . . Just tried to advocate KISS.

[bert]

Just tried to advocate KISS.

The management wrote: Out of consideration for fellow members, please avoid using phonetic abbreviations, such as "u" for "you" or "r" for "are".

How should I interprete KISS?

Regards Bert

[HW Mueller]

This has been sort of an exception, for obvious reasons: Keep it Simple, Stubid.

[tom jupille]

Good point, Bert. Although there is a certain irony in that HW is German.

I should apologize for the arcane "Soylent Green" reference. In case anyone is interested, the explanation is here: http://en.wikipedia.org/wiki/Soylent_Green

[HW Mueller]

I have seen (on both sides of the ocean!) so much mincing and/or slizing of whole or large parts of animals or biopsies of humans (including brain sections, etc.) that negative associations were not on my mind at all when I wrote the above.

[Mary Carson]

Some drugs ARE measured in whole blood. Rapamycin (Sirolimus) comes to mind--most published assays use whole blood hemolysate.

[HW Mueller]

Mary, what is the reason for using whole blood in those cases? Is it that somene believed it to be more appropriate or is there a rational (evidence based) reason? (The reason for my original post here was an attempt to point out that some people have legitimate, empirical, thought through, reasons for using this or that for doing their analyses).

[Mary Carson]

I didn't dig into this enough originally to find out for sure, but I always assumed it was because there was substantial cellular uptake of this drug. As someone already said, what chemist would use this matrix unless they had to?

A slightly more in depth search shows that was a good assumption:
"Because 95% of the drug is sequestered within erythrocytes,whole blood has been recommended as the sample matrix."
Yatscoff RW, Boeckx R, Holt DW, Kahan BD, LeGatt DF, Sehgal S, et al.
Consensus guidelines for therapeutic drug monitoring of rapamycin: report
of the consensus panel. Ther Drug Monit 1995;17:676–80.

[HW Mueller]

Ok, so someone didn´t just "feel" (or whatever) what´s appropriate, but used rational thinking based on some facts (knowledge).
In the case mentioned by you one wonders, though, whether this thinking goes far enough. If the drug has to pass into target cells without erythrocytes being sequestered there, then the equilibrium situation in the aqu. part or even in the albumin would be just as imporant, and analysis should then be done in all these parts. If the stuff worked by having the cells sequestered (maybe in the spleen) then it could well be sufficient to limit the analysis to the erythrocytes, which are easily separated.
This is just stated as a (probably) primitive example, sort of as an attempt, on my part, to continue to counteract the irrational gut decisions I have had to fight for the last ~30 years.