Bioequivalence and Bioavailability Forum

sambasivarao ☆ 2010-10-01 16:02 (5750 d 07:24 ago) Posting: # 5971 Views: 9,306	Appropriate Biological matrix for BA/BE studies [Bioanalytics] Post reply
	What are the basics to be consider to choose Biological matrix for BA/BE studies pharmacokinetics analysis? in other words What is the criteria to choose matrix (plasma/serum/blood/urine) for bioanalysis? Regards Sambasivarao Synapse Labs Ltd.

Helmut
★★★

Vienna, Austria,
2010-10-01 16:27
(5750 d 06:59 ago)

@ sambasivarao
Posting: # 5972
Views: 8,297

Appropriate Biological matrix for BA/BE studies

Post reply

Dear Sambasivarao!

❝ What is the criteria to choose matrix (plasma/serum/blood/urine) for bioanalysis?

Pharmacokinetics of the drug.
Bioanalytical constraints.

Urine is an acceptable matrix if the drug is mainly excreted unchanged renally. Due to improvements in bioanalysis urine is not a preferred matrix nowadays. If no characterization of the full time profile is possible (low concentrations in plasma) EMA recommends amount excreted in urine as the primary metric for extent of absorption, but still C_max from plasma.
Whole blood makes only sense if the drug is extensively bound to erythrocytes and essentially no concentrations would be found in plasma (one of the rare examples is chlorthalidone).
Serum or plasma makes no big difference - if the drug is stable enough. It takes some time until blood clotes; if you centrifuge too early most likely you will experience turbid serum after thawing. Therefore most analysts opt for plasma even if the drug is stable at room temperature. You have to check during method development which type of anticoagulant (heparin, citrate, different EDTA-salts) is suitable, i.e., does not interfere with the extraction, separation, and detection.

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Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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Ohlbe
★★★

France,
2010-10-01 16:39
(5750 d 06:47 ago)

@ Helmut
Posting: # 5973
Views: 8,142

Appropriate Biological matrix for BA/BE studies

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Dear all,

❝ Whole blood makes only sense if the drug is extensively bound to erythrocytes and essentially no concentrations would be found in plasma (one of the rare examples is chlorthalidone).

I think regulators would expect whole blood to be used for some drugs which are traditionally measured in whole blood for therapeutic drug monitoring, such as ciclosporin or tacrolimus, independently on whether they can nowadays be measured in plasma or not. Bortezomib would probably be a candidate for whole blood too.

Regards
Ohlbe

—
Regards
Ohlbe

Helmut ★★★ Vienna, Austria, 2010-10-01 16:46 (5750 d 06:40 ago) @ Ohlbe Posting: # 5974 Views: 8,131	TDM matrix Post reply
	Dear Ohlbe, THX, valuable advice! — Dif-tor heh smusma 🖖🏼 Довге життя Україна! Helmut Schütz The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes

Ohlbe ★★★ France, 2010-10-01 19:41 (5750 d 03:45 ago) @ Helmut Posting: # 5975 Views: 8,130	TDM matrix Post reply
	Dear Helmut, By the way, I checked on the FDA web site. They recommend whole blood for tacrolimus. I couldn't find a guidance for ciclosporin (I'm a bit surprised) or bortezomib (more recent drug). Regards Ohlbe — Regards Ohlbe

sambasivarao ☆ 2010-10-06 08:06 (5745 d 15:20 ago) (edited on 2010-10-06 10:11) @ Helmut Posting: # 6003 Views: 8,084	Appropriate Biological matrix for BA/BE studies Post reply
	Thank you very much for your valuable information Edit: Full quote removed. Please delete anything from the text of the original poster which is not necessary in understanding your answer; see also this post! [Ohlbe]

jchapdelaine ☆ 2011-02-03 19:08 (5625 d 03:18 ago) @ sambasivarao Posting: # 6549 Views: 7,654	Appropriate Biological matrix for BA/BE studies Post reply
	Is there any publications/literature on the acceptability of using serum or plasma for BE studies? I have an issue as the FDA recently posted a BE recommendation for an analyte stating the use of plasma, however we previously validated the assay using serum. Any help to justify this is welcomed.

Helmut
★★★

Vienna, Austria,
2011-02-05 20:11
(5623 d 02:15 ago)

@ jchapdelaine
Posting: # 6563
Views: 7,568

Serum vs. plasma

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Dear John,

please see the Policy.

❝ Is there any publications/literature on the acceptability of using serum or plasma for BE studies?

AFAIK no.

❝ I have an issue as the FDA recently posted a BE recommendation for an analyte stating the use of plasma,

I didn't check all 795 specific guidances, but the FDA seems to generally recommend plasma.

❝ […] however we previously validated the assay using serum.

I guess you don't want to ask FDA (might take ages to get a 'nonbinding' answer)?
From a PK point of view it makes absolutely no difference whether you analyze serum or plasma. Since you have a validated method, you obviously bypassed the drawbacks of using serum mentioned here. Method transfer from plasma to serum is easy, but the other way 'round cumbersome. :-(

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна!
Helmut Schütz

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Appropriate Biological matrix for BA/BE studies [Bioanalytics]

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Appropriate Biological matrix for BA/BE studies

Serum vs. plasma