Log in
Register|
Mithu ★ India, 2019-07-23 09:11 (1969 d 22:36 ago) Posting: # 20434 Views: 5,241 |
|
|
Dear All, please let me know under what condition, free and total analyte needs to be measured in biological fluids? this is especially became more difficult to us when label speak about free and total analyte but where the OGD does not speak about the same. Hope i am clear with my question. Regards Mithu |
|
Helmut ★★★   Vienna, Austria, 2019-07-23 13:06 (1969 d 18:42 ago) @ Mithu Posting: # 20436 Views: 4,471 |
|
|
Hi Mithu, ❝ please let me know under what condition, free and total analyte needs to be measured in biological fluids? Please define your terms. Are you referring by “free” to the fraction which is not protein-bound? Protein-binding is caused by Van-der-Waals forces which will be broken in any sample preparation (SPE, LLE, protein precipitation). Hence, what we measure is always the total analyte. If you are interested in protein-binding (not relevant in BE) go with equilibrium dialysis, ultrafiltration, ultracentrifugation. Or are you talking about a liposome-encapsulated drug (unencapsulated and encapsulated fractions)? The EMA and the FDA require both (examples: EMA, FDA*).
— Dif-tor heh smusma 🖖🏼 Довге життя Україна! ![[image]](https://static.bebac.at/pics/Blue_and_yellow_ribbon_UA.png) Helmut Schütz ![[image]](https://static.bebac.at/img/CC by.png) The quality of responses received is directly proportional to the quality of the question asked. 🚮 Science Quotes |
|
Mithu ★ India, 2019-07-23 15:32 (1969 d 16:16 ago) @ Helmut Posting: # 20437 Views: 4,489 |
|
|
❝ Please define your terms. Free analyte available in systemic Vs. Conjugated drug. ❝ Are you referring by “free” to the fraction which is not protein-bound? Yes. Here i am talking about Scopolamine Patch 1/72 hrs. The label is talking about free as well as total Scopolamine (free + conjugated analyte). SBOA contains study which was approved in 2015 does not contain any bifurcation of total or free Scopolamine measurement. As per my understanding, when half life is less i.e. <10 hrs and there is no major protein bounding, i believe what we are measuring is beyond the category of free or conjugated. As i believe, when there is a higher amount of protein binding, half life would be also high i.e. >20 hrs and more and clear information about drug conjugation should be defined. please correct me if my understanding is not correct. In such cases, where we have to measure free and total analyte, analytical methodology would also be different and must contain different extraction method to detect free as well as conjugated analyte. Here label says metabolize profile of Scopolamine is not fully characterized. Hope i could put my point in current manner and properly. Regards, Mithu |
|
nobody nothing 2019-07-24 12:45 (1968 d 19:02 ago) @ Mithu Posting: # 20439 Views: 4,417 |
|
|
protein binding has nothing to do with "conjugation" (typically used for phase 2 biotransformation reactions), as Helmut pointed out above it's only quickly reversible "binding" to protein components of blood/plasma. — Kindest regards, nobody |
|
Ladi ☆ Thailand, 2019-07-29 15:15 (1963 d 16:32 ago) @ Mithu Posting: # 20463 Views: 4,257 |
|
|
Hi Mithu, ❝ ❝ Are you referring by “free” to the fraction which is not protein-bound? ❝ ❝ Yes. ❝ ❝ Here i am talking about Scopolamine Patch 1/72 hrs. The label is talking about free as well as total Scopolamine (free + conjugated analyte). My understanding with conjugated analyte in this case is Scopolamine + 'a moiety' such as glucuronide moiety. Scopolamine dose have sulfate conjugated and glucuronide conjugated forms as its metabolites. So in this case free Scopolamine is the measurement of unconjugated Scopolamine only while total Scopolamine is the measurement of free Scopolamine + deconjugated Scopolamine (after some hydrolysis reactions). Similar case with Ezetimibe. I think nothing have to do with protein binding here. This journal talks about the free and conjugated Scopolamine>> https://www.ncbi.nlm.nih.gov/pubmed/18970269 Making sense? Ladi |
|
Mithu ★ India, 2019-08-03 12:41 (1958 d 19:07 ago) @ Ladi Posting: # 20468 Views: 4,180 |
|
|
❝ This journal talks about the free and conjugated Scopolamine>> https://www.ncbi.nlm.nih.gov/pubmed/18970269 thank you. Regards, Mithu |
Ing. Helmut Schütz