seeker-seventy-six
New Member
I've done some initial research into how the supply chain is distributed in terms of salt forms, but it's all very opaque. Looking for some editorial/comments on findings so far. I think next steps are reaching out to vendors about this particular ion chromatography test family and doing some sample tests myself.
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How do I know if I'm getting tirzepatide base form or tirzepatide salt form?
The TLDR is that you don't know unless you do another specific test in the ion chromatography family which is not included in the typical purity/mass tests of GBs. Most of what's being sold “grey” at the prices we’re seeing is going to be tirzepatide salt form. Further testing across the supply would be needed to understand the distribution of the counterions salt form used - tirzepatide sodium, tirzepatide acetate, etc.
From PeptideTests
We use tirzepatide sodium as the reference standard for assay (content)
Purity does not use a standard [value], it's a sum of all non-tizepatide peaks divided by the tirzepatide peak in the sample
You cannot tell if a reconstituted solution is tirzepatide sodium or acetate without testing. We don't currently offer this type of test.
From Janoshik
> When testing purity, do you differentiate which [form] the sample is compared against?
Base, as we use NET PEPTIDE CONTENT (which disregards counterions)
> Are the base vs salt form even discernable once reconstituted into solution?
No, without testing specifically for the counterion
> And is there a test to determine which salt form and cation was used to manufacturer the tirzepatide sample?
Yes, ion chromatography, testing for presence
Fluorine NMR for TFA, EDX / Atomic Absorption Spectrometry for Sodium
H/C NMR for Acetate
Etc. for other counterions
Jonoshik offers this type of testing
Do I need to worry about taking tirzepatide in salt form?
The honest answer is that the salt forms have no published papers available comparing the differences of bioavailability/efficacy/safety. Only the tirzepatide base form was used in FDA trials.
Most in this community will say that the tirzepatide salt form is exactly the same as the tirzepatide base form once reconstituted in BAC water since once dissolved the salt counterions chemically “pop off” into the water leaving tirzepatide base and the “popped off” counterion (eg. Sodium, acetate, or whichever counterion was ionically bonded to the tirz peptide)
The reality is that while salt forms are widely used in many other medications (salt forms account for over 50% of pharmaceuticals), being in a salt form can change the bioavailability, pH in solution, or lipophilicity, and choosing the appropriate counterion to make the ionic bond with the peptide can affect these things which can also have an effect on injection site irritation. And different salt forms can have different effects. Researchers should be cautious in assuming therapeutic equivalence among different salt forms. Source
From anecdotal evidence of testing facilities using tirzepatide sodium salt form as the comparison source of truth source, and the cheap cost of manufacturing the salt version, it's likely what's most readily available on the grey market these days are tirzepatide sodium and tirzepatide acetate. Which means when you reconstitute your tirzepatide in BAC water, you're getting
Tirzepatide Sodium -> Tirzepatide base + Sodium , or
Tirzepatide Acetate -> Tirzepatide base + Acetic Acid
in each of your recon vial.
But there are several salt forms that exist in the peptide world:
Sodium Salt: Formed with sodium (Na+)
• Usage: Used in various injectable solutions to maintain osmotic balance.
• Safety: Safe in controlled amounts, but excessive sodium can lead to health issues. At tirzepatide doses this is not an issue.
Acetate Salt: Formed with acetic acid; widely used due to its biocompatibility.
• Usage: Common in both pharmaceuticals and supplements.
• Safety: Typically safe for human use when properly formulated and administered.
Hydrochloride Salt: Formed with hydrochloric acid; increases solubility but may require pH adjustment.
• Usage: Widely used in medications due to their good solubility in water.
• Safety: Generally considered safe when used as directed in approved medications, but may require pH adjustment for comfortable subQ injection.
Trifluoroacetate Salt: Common in peptide synthesis but may need to be exchanged due to potential biological effects.
• Usage: Often used in peptide synthesis.
• Safety: Not recommended for human use as TFA can be toxic. Peptides sold for human use are purified to remove TFA residues.
Formate Salts
• Usage: Less common in pharmaceuticals.
• Safety: Limited data on safety for human injection; should be used with extreme caution.
Further research and testing is needed to understand the real distribution of t
he tirzepatide salt forms available on the grey market.
----------------
How do I know if I'm getting tirzepatide base form or tirzepatide salt form?
The TLDR is that you don't know unless you do another specific test in the ion chromatography family which is not included in the typical purity/mass tests of GBs. Most of what's being sold “grey” at the prices we’re seeing is going to be tirzepatide salt form. Further testing across the supply would be needed to understand the distribution of the counterions salt form used - tirzepatide sodium, tirzepatide acetate, etc.
From PeptideTests
We use tirzepatide sodium as the reference standard for assay (content)
Purity does not use a standard [value], it's a sum of all non-tizepatide peaks divided by the tirzepatide peak in the sample
You cannot tell if a reconstituted solution is tirzepatide sodium or acetate without testing. We don't currently offer this type of test.
From Janoshik
> When testing purity, do you differentiate which [form] the sample is compared against?
Base, as we use NET PEPTIDE CONTENT (which disregards counterions)
> Are the base vs salt form even discernable once reconstituted into solution?
No, without testing specifically for the counterion
> And is there a test to determine which salt form and cation was used to manufacturer the tirzepatide sample?
Yes, ion chromatography, testing for presence
Fluorine NMR for TFA, EDX / Atomic Absorption Spectrometry for Sodium
H/C NMR for Acetate
Etc. for other counterions
Jonoshik offers this type of testing
Do I need to worry about taking tirzepatide in salt form?
The honest answer is that the salt forms have no published papers available comparing the differences of bioavailability/efficacy/safety. Only the tirzepatide base form was used in FDA trials.
Most in this community will say that the tirzepatide salt form is exactly the same as the tirzepatide base form once reconstituted in BAC water since once dissolved the salt counterions chemically “pop off” into the water leaving tirzepatide base and the “popped off” counterion (eg. Sodium, acetate, or whichever counterion was ionically bonded to the tirz peptide)
The reality is that while salt forms are widely used in many other medications (salt forms account for over 50% of pharmaceuticals), being in a salt form can change the bioavailability, pH in solution, or lipophilicity, and choosing the appropriate counterion to make the ionic bond with the peptide can affect these things which can also have an effect on injection site irritation. And different salt forms can have different effects. Researchers should be cautious in assuming therapeutic equivalence among different salt forms. Source
From anecdotal evidence of testing facilities using tirzepatide sodium salt form as the comparison source of truth source, and the cheap cost of manufacturing the salt version, it's likely what's most readily available on the grey market these days are tirzepatide sodium and tirzepatide acetate. Which means when you reconstitute your tirzepatide in BAC water, you're getting
Tirzepatide Sodium -> Tirzepatide base + Sodium , or
Tirzepatide Acetate -> Tirzepatide base + Acetic Acid
in each of your recon vial.
But there are several salt forms that exist in the peptide world:
Sodium Salt: Formed with sodium (Na+)
• Usage: Used in various injectable solutions to maintain osmotic balance.
• Safety: Safe in controlled amounts, but excessive sodium can lead to health issues. At tirzepatide doses this is not an issue.
Acetate Salt: Formed with acetic acid; widely used due to its biocompatibility.
• Usage: Common in both pharmaceuticals and supplements.
• Safety: Typically safe for human use when properly formulated and administered.
Hydrochloride Salt: Formed with hydrochloric acid; increases solubility but may require pH adjustment.
• Usage: Widely used in medications due to their good solubility in water.
• Safety: Generally considered safe when used as directed in approved medications, but may require pH adjustment for comfortable subQ injection.
Trifluoroacetate Salt: Common in peptide synthesis but may need to be exchanged due to potential biological effects.
• Usage: Often used in peptide synthesis.
• Safety: Not recommended for human use as TFA can be toxic. Peptides sold for human use are purified to remove TFA residues.
Formate Salts
• Usage: Less common in pharmaceuticals.
• Safety: Limited data on safety for human injection; should be used with extreme caution.
Further research and testing is needed to understand the real distribution of t
he tirzepatide salt forms available on the grey market.
