Bacterial Endotoxins are ubiquitous/in everything. To my knowledge you can't completely eliminate them.
Therefore they are a definite consideration for anything injectable. And even more so if something is for IV administration.
And if the dose is high (in mg not mcg) then you really need to be careful as Endotoxins are usually equated/denominated to mcg, and obviously if you're injecting 25 mg, it's 25000 mcg, and if something is even 0.5 EU/mcg, then.. 25000 x 0.5 = 12500 Endotoxin units.
It easily adds up.
Endotoxins cause 'endotoxemia' and septic shock and maybe death if you're unlucky.
If I recall correctly, safe human exposure via injection (non IV) should be below 200 or 300 EU (endotoxin units) per day or dose (not sure).
The FDA has set an endotoxin limit for all injectable drugs, including Water/Saline for Injections. There is some discussion about limits/calculations on the following page:
http://www.fda.gov/I...s/ucm072918.htm
You're right to get TFA removed. TFA is toxic to cells, but it is not known how toxic to cells in the context of long-term human administration/exposure, because obviously it's not used for pharma drugs.
Usually drug API's are as Acetate, Chloride, or Sodium salts because they are physiologically compatible.
I'm enthralled by the "Research Peptide" experiment going on, cause 99% of them will be as TFA salt (not to mention the Endotoxins).
I eager to see if after a few more years of use (on top of the time elapsed thus far) whether people start reporting ill heath effects which trace back to cell toxicity/death via TFA in the 'Research Peptides' they've been using.
If they don't then I know I can stop spending extra to get GMP like peptides. As you would know, to remove TFA and switch to Acetate costs about 40% extra because peptide is lost in the process, as well as the extra labour time involved.
Is bacterial endotoxin a worry in synthetic peptides built on resin? I thought its just an issue when a protein was made via genetic modification of eg. E.coli. b-NGF comes to mind in this case.
I'll definitely look at Pivotal Bioscience next time.
Edited by pure, 20 March 2016 - 01:21 PM.