Coming back to: Washout: how long is long enough, and for what purpose

Posting this under the heading it deserves: Washout: how long is long enough, and for what purpose Everything below is what sits behind that.

Working through the identity arithmetic and I would like it checked.

retatrutide has a monoisotopic mass close to 4731.3 Da. On an electrospray instrument I would expect to see the multiply charged series rather than the intact singly charged ion, so for the doubly charged species I calculate (4731.3 + 2 x 1.00728) / 2, and for the triply charged the analogous expression.

The observed values in the report sit within a few ppm of those. My question is what that actually establishes, because I have seen people treat a mass match as a purity result and I do not think it is one.

Albumin binding: semaglutide binds albumin through a fatty side chain, which sequesters the free form and extends the half-life. Tirzepatide also has albumin binding (different mechanism) which extends its half-life compared to an unmodified peptide.

Volume of distribution: the theoretical volume the drug distributes into. For albumin-binding compounds, volume is reduced compared to drugs that do not bind protein. That is relevant to understanding how much free drug is available.

On post #42 — agreed on the reasoning, with one qualification.

Albumin binding: semaglutide binds albumin through a fatty side chain, which sequesters the free form and extends the half-life. Tirzepatide also has albumin binding (different mechanism) which extends its half-life compared to an unmodified peptide.

Hepatic metabolism: the degree to which each compound is hepatically metabolised versus renally cleared is known but varies. Severe liver disease changes clearance.

Two things before anyone answers the substance.

First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound.

Two things before anyone answers the substance.

First, the context in the first post is clear and specific. Second, the question is framed so that an answer can actually address it. Both are the norm here and both matter more than they sound.

Coming back to post #114, because the follow-up matters more than the original answer.

Half-life: semaglutide ≈ 165–184 hours (about a week). Tirzepatide ≈ 5 days. Liraglutide ≈ 13 hours. The half-life determines how much accumulation happens at steady state and how long it takes to clear after stopping.

I read post #136 twice before replying, because I had assumed the opposite.

SNAC (the oral bioavailability enhancer): sodium N-(8-[2-hydroxybenzoyl]amino) caprylate transiently raises gastric pH and promotes absorption. Without it, oral bioavailability is too low for clinical use. With it, bioavailability is still variable between people.