cloudy reta (I have good BAC)
- Thread starter ambot88
- Start date
I haven't tried straight up PBS, is that safe to inject? what would it's shelf life be?
My post above says that PBS is the only way to correct the vial by stabilizing the environment for Reta and it dissipates the residual salts. Once that's done, the Reta is as safe as it's going to be. I've attached the entire comment on how to remediate the salts issue. He suggests straight BA (Benzyl alcohol) at 8 IU to replace the BAC. Unless you have BA handy, that's not feasible, and we already know that BAC doesn't help. So it's a trade off. Lower shelf life for a more stable peptide. I don't know your dosage, but I'm at 10 mg so that's two weeks of peptide. You'll have to make that decision.
EDIT: one important question that isn't answered, is what does that trip to lower pH do to Reta in terms of degradation. We already know it's more prone to losing amino bonds than Tirz and other peptides under stress. Only testing will answer that question.
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TooBigtoFail
GLP-1 Enthusiast
Based on posts from past 2 years, 'cloudy' due to pH, can be corrected. Some peptides require some AA to avoid the issue. Did you measure the pH after adding bac? and pH of the bac itself?
Hospira pH average is 5.7 but can vary between 4.5 to 7.0pH (this is from Pfizer's own tech sheet). They do not list using hydrochloric acid and/or sodium hydroxide for pH adjustment, thus the pH variation.
If your reta pH is also 'off', acidic, I am not surprise you get precipitation. Maybe first add Sodium Bicarbonate (not AA) to your bac to increase pH before you recon. Novo and E. Lilly list their excipients and I try to mimic their formula. Also, their reta has no Sodium Chloride. Tirz does list Sodium Chloride. Others have posted not to use BAC Sodium Chloride with reta as they reported cloudiness.
I have to say that my main reason for throwing away 6-8% of my vials in past 2 years was due to vials with no vacuum (CN suppliers). And in one of those case, the recon had become cloudy.
No more vacuum issues since I switched to Nex. Good luck. I would not use a cloudy recon (as mentionned on many medical sites). Not even after filtering it.
Hospira pH average is 5.7 but can vary between 4.5 to 7.0pH (this is from Pfizer's own tech sheet). They do not list using hydrochloric acid and/or sodium hydroxide for pH adjustment, thus the pH variation.
If your reta pH is also 'off', acidic, I am not surprise you get precipitation. Maybe first add Sodium Bicarbonate (not AA) to your bac to increase pH before you recon. Novo and E. Lilly list their excipients and I try to mimic their formula. Also, their reta has no Sodium Chloride. Tirz does list Sodium Chloride. Others have posted not to use BAC Sodium Chloride with reta as they reported cloudiness.
I have to say that my main reason for throwing away 6-8% of my vials in past 2 years was due to vials with no vacuum (CN suppliers). And in one of those case, the recon had become cloudy.
No more vacuum issues since I switched to Nex. Good luck. I would not use a cloudy recon (as mentionned on many medical sites). Not even after filtering it.
I have a question about the AA save now, I added a drop on AA to my cloudy reta and immediately it kind of separated and had a bunch of visible particles but after about 15 minutes they had all dissipated and the solution was clear. Do you think the clumping ruined the reta or do you think it's okay now? The PBS rescued vials are not staying clear.
Victorhouston
GLP-1 Novice
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I had a similar scenario last month, after bumping around a few other sites and groups I found out others had encountered this same issue and a majority of those others actually still used it, I used it as well and it's still as effective as if it were to be clear but that's just me..
You can't know for sure without testing, but what I've read is that the Reta is still fine. I asked Gemini if AA would compromise the Reta and got the below. This is at up to one drop per mL, up to a 5% AA solution.
Will the Retatrutide be Compromised?
Generally, no. Retatrutide and similar GLP-1 analogues are relatively stable in slightly acidic environments.
Structural Integrity: Peptides are often stored as TFA salts specifically because they are more stable in an acidic state. Bringing the pH down to a range of 4.0 to 6.0 is standard for many injectable peptide formulations.
Bioavailability: Once injected, the body’s natural buffering system (the bicarbonate buffer) immediately neutralizes the small amount of acid, and the peptide performs as intended.
Injection Comfort: The primary "compromise" is not to the peptide, but to the user. A lower pH can cause a temporary stinging or burning sensation at the injection site.
Thanks chili! I'll give it a try and hope for the best
so you just straight up used the cloudy reta and it was fine? good to know.
Victorhouston
GLP-1 Novice
🚫No Source Discussion🚫
correct, will be taking my 3rd dose this Tuesday coming up and the weight is still steadily dropping
upinsmoke
Recently Joined
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I have been searching for threads when it comes to cloudiness and potential fixes and what not. This is all still pretty new to me, so trying to prepare for situations that may come up.
I have some stuff stored that my subjects need to start, and would prefer sooner rather than later, but I have decided that until I have the stuff to filter properly, it can wait. Which is on it's way, stuck in bloody customs.
But pinning cloudy stuff, is next level gutsy in my opinion. Courage on another level !!! That's not in a bad way, that's more like "Not all heroes wear capes" way. 🤣.
Like they say, you eat with your eyes. That's sort of me. Could be the best tasting stuff you ever eat, but if it looks like turd on a plate, I'm about 80% mind made up. When it comes to subject testing and seeing it cloudy without a fix. I'm pretty much got my mind made up that I am cutting losses.
!00% applaud the dedication. 😁👍
Nerker
GLP-1 Apprentice
Watching the ERP TG // PBS talk also. Got some RT20's coming. Will advise when I recon.
Jone5y87!
GLP-1 Apprentice
Is is still safe to pin if cloudy ?
GusGustavson
Recently Joined
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Commenting because I saw other people mentioning this problem too.
Some science behind it. Maybe interesting for others who have had this happen or if it ever happens in the future. The cloudiness is likely a pH problem. The peptide likely has residual TFA salts from manufacturing that should not be there, and when BAC water is added the combined acidity lands right on retatrutide's isoelectric point. The molecules lose their charge, clump together, and crash out of solution. That's the cloud.
The simplest thing to rule out is the BAC water itself. Hospira's own spec allows pH from 4.5 to 7.0, which is a huge range. A bottle sitting at the low end will crash TFA laden peptide while a bottle at the high end might reconstitute it perfectly clear.
Trying BAC water from a different supplier or at least a different production lot is the most practical first step before reaching for any other options. With pH strips it is possible to compare different BAC bottles and see if it explains the cloudiness.
Also worth noting that Hospira is one of the most counterfeited medical products out there. If it's fake and actually contains sodium chloride, that causes a whole different precipitation problem, and switching supplier would immediately reveal that.
And filtering a cloudy solution removes the peptide itself, not some contaminant. That cloud IS the retatrutide. A significant portion of the dose can be lost with no way of knowing how much. Filtering only makes sense after the solution has already been cleared through a pH correction, to remove the small fraction of irreversible aggregates.
The PBS rescue not staying clear is because aggregate seeds formed while the peptide sat at the wrong pH. Those seeds act as templates that slowly pull dissolved peptide back out of solution. Adding more PBS won't fix that because it's a structural problem not a pH problem at that point.
Acetic acid can make it look clear but the initial clumping that was visible was further aggregation before redissolving. Some peptide was likely damaged irreversibly, and the solution is now in a more acidic environment that degrades it faster over time.
The longer a reconstituted peptide sits at the wrong pH the more irreversible damage accumulates.
Worth keeping in mind that a reship from the same vendor doesn't necessarily solve anything if the replacement comes from the same batch. The TFA salt issue is at the production level, not the individual vial level. If the washing step was insufficient for that batch, every vial from it carries the same excess TFA. Whether it shows as cloudiness can depend on where your BAC water lands on the pH scale.
Would I use cloudy solution? No.
Aggregated peptide can train the immune system to recognize that peptide as a threat. Once antibodies develop against it, they can neutralize not just the aggregated form but also properly dissolved peptide in future injections. Pinning cloudy product can in theory make clean product less effective later.
Some science behind it. Maybe interesting for others who have had this happen or if it ever happens in the future. The cloudiness is likely a pH problem. The peptide likely has residual TFA salts from manufacturing that should not be there, and when BAC water is added the combined acidity lands right on retatrutide's isoelectric point. The molecules lose their charge, clump together, and crash out of solution. That's the cloud.
The simplest thing to rule out is the BAC water itself. Hospira's own spec allows pH from 4.5 to 7.0, which is a huge range. A bottle sitting at the low end will crash TFA laden peptide while a bottle at the high end might reconstitute it perfectly clear.
Trying BAC water from a different supplier or at least a different production lot is the most practical first step before reaching for any other options. With pH strips it is possible to compare different BAC bottles and see if it explains the cloudiness.
Also worth noting that Hospira is one of the most counterfeited medical products out there. If it's fake and actually contains sodium chloride, that causes a whole different precipitation problem, and switching supplier would immediately reveal that.
And filtering a cloudy solution removes the peptide itself, not some contaminant. That cloud IS the retatrutide. A significant portion of the dose can be lost with no way of knowing how much. Filtering only makes sense after the solution has already been cleared through a pH correction, to remove the small fraction of irreversible aggregates.
The PBS rescue not staying clear is because aggregate seeds formed while the peptide sat at the wrong pH. Those seeds act as templates that slowly pull dissolved peptide back out of solution. Adding more PBS won't fix that because it's a structural problem not a pH problem at that point.
Acetic acid can make it look clear but the initial clumping that was visible was further aggregation before redissolving. Some peptide was likely damaged irreversibly, and the solution is now in a more acidic environment that degrades it faster over time.
The longer a reconstituted peptide sits at the wrong pH the more irreversible damage accumulates.
Worth keeping in mind that a reship from the same vendor doesn't necessarily solve anything if the replacement comes from the same batch. The TFA salt issue is at the production level, not the individual vial level. If the washing step was insufficient for that batch, every vial from it carries the same excess TFA. Whether it shows as cloudiness can depend on where your BAC water lands on the pH scale.
Would I use cloudy solution? No.
Aggregated peptide can train the immune system to recognize that peptide as a threat. Once antibodies develop against it, they can neutralize not just the aggregated form but also properly dissolved peptide in future injections. Pinning cloudy product can in theory make clean product less effective later.
RetaScrub
Recently Joined
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This is my question as well. I understand the TFA is neutralized at the higher pH from the PBS, but wouldn’t the TFA still be present, and still have some injection risk?
That's my remaining question also. You would think correcting the environment wouldn't be all there is to it, but that's what Gemini says. I need to ask a chemist guy I know to clarify this.
RetCurious
GLP-1 Enthusiast
TFA salts you say?
German Chemicals Office Submits Proposal to EU Linking TFA to Reproductive Toxicity
German Chemicals Office Submits Proposal to EU Linking TFA to Reproductive Toxicity
TFA, an atmospheric by-product of HFO-1234yf and other f-gases, is considered by scientists to be a PFAS that persists in the environment.
naturalrefrigerants.com
agussie
GLP-1 Apprentice
I mean they’re everywhere including the rain, lakes, etc. I agree, they’re not considered good, as they line right up with the other forever chemical PFAS.TFA salts you say?
German Chemicals Office Submits Proposal to EU Linking TFA to Reproductive Toxicity
German Chemicals Office Submits Proposal to EU Linking TFA to Reproductive Toxicity
TFA, an atmospheric by-product of HFO-1234yf and other f-gases, is considered by scientists to be a PFAS that persists in the environment.
RetCurious
GLP-1 Enthusiast
Do you think Lilly is using TFA in the process for their products?
Looks like they probably do.
"To make sure no unwanted chemical reactions occur, so called "chemical locks" are created, which need to be removed at the end of the process. In nearly all peptide synthesis the substance used for removing these “chemical locks” is TFA."
PFAS enabling the synthesis of therapeutic peptides - FPP4EU
Therapeutic peptides are a promising and novel approach to treat many diseases including cancer, cardiovascular and autoimmune diseases.
www.fpp4eu.eu
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RetCurious
GLP-1 Enthusiast
Maybe I should ask if Ely Lilly would have checks in place to prevent the TFA contamination?
I think what I'm getting at is I wouldn't knowingly inject that into my body even if it can be cleared up visibly it doesn't remove the problem.
I think what I'm getting at is I wouldn't knowingly inject that into my body even if it can be cleared up visibly it doesn't remove the problem.
