中国产Tirz的质量与礼来相比如何?

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deleted.user.18 said:
I didn’t think you were flippant at all. Hopefully you didn’t take my comment as anything other than further engagement.

The peppys post blew my brain up. The guys discussing it must have phds or something.

I wasn’t sure 🙃 All is well. I look forward to post at Peppy’s.

Yes, there’s a lot that gray circumvents. Makes sense that a finished product that must meet regulation needs more details carefully handled than “just” a peptide being shipped.

Ah the wormhole opens.
 
joseblo said:
Most of the compounders buy from China and recon anyway. If they're spouting off BS, I lose even more trust in them.

There are some differences that the others have mentioned (testing, constant dose, purity, B12 etc) and there are others like the "free" autopen, more preservatives for room temp shipping, and a freebase form rather than acetate that the grey market provides. Manufacturing for LL is likely significantly different just due to scale, and of course there's not a lyophilization and recon steps.

Does it work the same? If it's pure and has the right concentration, Yep!
I came here looking for exactly something like this comment. @joseblo How is it that we know that the counterion of the form we are receiving is acetate?

Do we know how the synthesis is purportedly done? Ie, Is it still the original solid phase synthesis using TFA then ion exchange to sub in acetate, or neutralize with NaOH and leave Na… or the hybrid solid/liqiid phase (that I known nothing about other than those words?)

I’m not actually contesting that gray Tirz works for weight, and that the salt in the correct pH solution dissociates to yield the base, but I’m wondering if we’re always receiving the base with the same counter ion or other non-peptide production molecules that might end up in the mix, yet not be visible in HPLC-mass spec purity testing. (Assuming janoshik and the like use HPLC mass spec)

Looking for someone who has looked into this to help me understand, please 🙂 I think this is very relevant to @Gr33dyOctopus’ question. Because this could make the soup that we recon a different compound. I am very interested in this because I’m in glps primarily for the less publicized benefits. Also maybe if our subcutaneous pH is not the appropriate pH to free the base, maybe it’s better to buffer the recon…

joseblo said:
Most of the compounders buy from China and recon anyway. If they're spouting off BS, I lose even more trust in them.

There are some differences that the others have mentioned (testing, constant dose, purity, B12 etc) and there are others like the "free" autopen, more preservatives for room temp shipping, and a freebase form rather than acetate that the grey market provides. Manufacturing for LL is likely significantly different just due to scale, and of course there's not a lyophilization and recon steps.

Does it work the same? If it's pure and has the right concentration, Yep!
 
deleted.user.18 said:
There is an interesting post on peppys that covers the finer points of the science of this stuff. There’s more than just the API in the vial, and it all has a role. Formulation is more complicated than most of us will ever wrap our heads around.
Do those science guys say in the end what difference it makes, and if we can even figure out what’s being sold?

Also imma going to see what peppy’s is, any tips how to find that post you’re referring to?
 
Labcat said:
I came here looking for exactly something like this comment. @joseblo How is it that we know that the counterion of the form we are receiving is acetate?

Do we know how the synthesis is purportedly done? Ie, Is it still the original solid phase synthesis using TFA then ion exchange to sub in acetate, or neutralize with NaOH and leave Na… or the hybrid solid/liqiid phase (that I known nothing about other than those words?)

I’m not actually contesting that gray Tirz works for weight, and that the salt in the correct pH solution dissociates to yield the base, but I’m wondering if we’re always receiving the base with the same counter ion or other non-peptide production molecules that might end up in the mix, yet not be visible in HPLC-mass spec purity testing. (Assuming janoshik and the like use HPLC mass spec)

Looking for someone who has looked into this to help me understand, please 🙂 I think this is very relevant to @Gr33dyOctopus’ question. Because this could make the soup that we recon a different compound. I am very interested in this because I’m in glps primarily for the less publicized benefits. Also maybe if our subcutaneous pH is not the appropriate pH to free the base, maybe it’s better to buffer the recon…
I'm not that kind of chemist, but there are posts other places where people with more knowledge than I suggest that the for the scales and equipment that is available, Solid Phase Synthesis remains the most cost effective method at small /med scales. It is possible to test for counter ion among a giant list of possible contaminants and it's been done. Things like this along with degradation and multi-peptide interactions are studied by the community. There are more tests than just HPLC-MS in use, that just happens to be the most common and convenient.

My take from a manufacturing standpoint is that although there are screw ups that can be made in raw peptides (it looks like some Survo with wrong/no counter ion recently was), it's rare for the majors to do that (note that it doesn't recon correctly and was caught immediately) and they lose money and face on it. The bigger more common mistakes (wrong peptide, over/under mass, bad lyo) are done by the little guys, because they aren't pros and have to do a zillion different things. The good news with testing the way it is that most of these folks (not TikTok) get busted and lose quickly or have to change names regularly. Of course, you could just get the wrong product if you don't use the popular well tested vendors, or get rug-pulled even if you do.

Look for the most likely mistakes. You're more likely to find your keys next to your car or bar stool, rather than under the streetlight. With their larger scale, compounders could provide better testing and sterility even for Grey when they expected long term profits, high margins, and worried about audits. Now they just have experience and facilities, but frankly less motivation with pharma litigation as their biggest risk. Pharma has a whole other set of risks and rewards, but the combination of experience, facilities, scale, and incentives means they probably won't screw up the basics (they'll get clever and bean counters will try to increase profits and marketing will push for some crazy complicated thing that will blow up).

edited for spelling/grammar
 
Gr33dyOctopus said:
Is there a huge difference? On the comppunding forums they say that Lilly has better ingredients, equipment and facilities that put Chinese tirz to shame.

And tthat the gray we get is basically junk. I argued that compound tirz is all from China too, and even though there's a green list of precursors compounding pharmacies can buy from, not a single one is in the country.

Over on reddit we also saw lilly tirz pens that were made in and shipped from China. So.... how big a difference really is gray market tirz from lilly tirz when it comes down to actual brass tacks?

My own experience, having taken brand name tirzepatide many times along with Chinese tirzepatide many times is that there is no noticeable difference. My own experience seems to be the most common of those who have tried both, based upon the forums that I have read. I'm confident that in terms of product uniformity and in terms of being sanitary, the stuff from Eli Lilly is far better than the gray stuff. If anyone any expects that the Chinese factories are models of sanitariness, you are likely mistaken. The FDA approved factories in China that the compounded pharmacies are supposed to use may be more sanitary. I am only willing to use gray stuff because lyophilized peptides injected subcutaneously pose little risk even when made under less than ideal conditions.
 
Gr33dyOctopus said:
Is there a huge difference? On the comppunding forums they say that Lilly has better ingredients, equipment and facilities that put Chinese tirz to shame.

And tthat the gray we get is basically junk. I argued that compound tirz is all from China too, and even though there's a green list of precursors compounding pharmacies can buy from, not a single one is in the country.

Over on reddit we also saw lilly tirz pens that were made in and shipped from China. So.... how big a difference really is gray market tirz from lilly tirz when it comes down to actual brass tacks?

Some of the compounding pharmacies turned out to be just buying unapproved stuff from China.
 
Gr33dyOctopus said:
Is there a huge difference? On the comppunding forums they say that Lilly has better ingredients, equipment and facilities that put Chinese tirz to shame.

And tthat the gray we get is basically junk. I argued that compound tirz is all from China too, and even though there's a green list of precursors compounding pharmacies can buy from, not a single one is in the country.

Over on reddit we also saw lilly tirz pens that were made in and shipped from China. So.... how big a difference really is gray market tirz from lilly tirz when it comes down to actual brass tacks?

I'll mention one advantage brand name has over grey at least if you use the pen: It's almost impossibly to get the dosing wrong.

Now here is an advantage from grey that you won't get from the pens: You control the dose. You can take it more than once per week in order to keep the amount in your body more stable. You can also decide to raise or lower the dose in increments small than 2.5 mg per week.
 
keangkong said:
Some of the compounding pharmacies turned out to be just buying unapproved stuff from China.
Ugh. I saw a summary of an fda 483 from a big 503b saying they weren’t buying from an approved fda bulk supplier (this was before the tirz is no longer in shortage announcement mar ‘25.)
 
joseblo said:
I'm not that kind of chemist, but there are posts other places where people with more knowledge than I suggest that the for the scales and equipment that is available, Solid Phase Synthesis remains the most cost effective method at small /med scales. It is possible to test for counter ion among a giant list of possible contaminants and it's been done. Things like this along with degradation and multi-peptide interactions are studied by the community. There are more tests than just HPLC-MS in use, that just happens to be the most common and convenient.

My take from a manufacturing standpoint is that although there are screw ups that can be made in raw peptides (it looks like some Servo with wrong/no counter ion recently was), it's rare for the majors to do that (note that it doesn't recon correctly and caught immediately) and they lose money and face on it. The bigger more common mistakes (wrong peptide, over/under mass, bad lyo) are done by the little guys, because they aren't pros and have to do a zillion different things. The good news with testing the way it is that most of these folks (not TikTok) get busted and lose quickly or have to change names regularly. Of course, you could just get the wrong product if you don't use the popular well tested vendors, or get rug-pulled even if you do.

Look for the most likely mistakes. You're more likely to find your keys next to your car or bar stool, rather than under the streetlight. With their larger scale, compounders could provide better testing and sterility even for Grey when they expected long term profits, high margins, and worried about audits. Now they just have experience and facilities, but frankly less motivation with pharma litigation as their biggest risk. Pharma has a whole other set of risks and rewards, but the combination of experience, facilities, scale, and incentives means they probably won't screw up the basics (they'll get clever and bean counters will try to increase profits and marketing will push for some crazy complicated thing that will blow up).
唉,我完全不懂化学,所以我觉得你还是比我强。你说的有道理,有些东西是可以测试的,也许我们没测试是因为目前为止一切正常。

研究级固相合成试剂中的TFA反离子似乎是一个特别容易出问题的点,研究级产品需要自行清洗,所以即使是转售给我们的人,也可能因为疏忽而没有彻底清洗干净。

我很好奇你有多确定我们拿到的是乙酸盐?

我看到一篇很有意思的文章,说TFA是一种永久性化学物质,可能会对肝脏和生殖系统造成影响。我年纪大了,但我相信你们大多数人都希望自己能长寿并繁衍后代。

https://chemtrust.org/tfa-everywhere-and-forever-faq/

或许我们已经达到了最佳状态,拥有一个可以进行群体测试的社群。在市场力量导致供应出现更糟糕的情况之前,我们正处于一个尚未被充分认识的黄金时代。
 
这个帖子信息量很大。

但我在阅读的时候一直在想,你知道燕麦粥里有少量老鼠屎是可以接受的吗?
 
Sasquatch said:
这个帖子信息量很大。

但我在阅读的时候一直在想,你知道燕麦粥里有少量老鼠屎是可以接受的吗?
它可能会改变燕麦片的冰点。🤣

你说的我们能耐受一定量,而且运气好的话确实有道理。但在美国农业部标准出台之前,所有东西里都含有大量的鼠粪。

不过,我的最终目标是对肽的残留效力有一个合理的预期。我愿意根据效果调整剂量,但出于其他健康原因,如果肽的效力较弱,我真的不想因为不小心增加剂量而产生不良反应。
 
Labcat said:
那些搞科学的人最后会说这到底有什么区别吗?我们能不能搞清楚他们卖的到底是什么?

还有,我想看看Peppy's是什么,有什么办法能找到你说的那个帖子吗?
如果您是会员且拥有足够的权限,请查看此帖: https://chat.peppys.org/t/peptide-quality/42997/23
 
Labcat said:
我来这里就是想找类似这样的评论。 @joseblo 我们怎么知道我们收到的这种形式的抗衡离子是乙酸根离子呢?

我们知道它是如何合成的吗?也就是说,它还是最初的固相合成法,先用三氟乙酸盐(TFA)反应,然后通过离子交换置换乙酸根离子,还是用氢氧化钠(NaOH)中和后留下钠离子……还是混合固液相合成法(除了这些词之外,我对它一无所知)?

我并不是质疑灰色Tirz的重量,也不是质疑盐在合适的pH溶液中会解离生成碱,但我怀疑我们收到的碱是否总是带有相同的抗衡离子,或者是否混入了其他非肽类生产分子,而这些分子在高效液相色谱-质谱(HPLC-MS)纯度测试中却检测不出来。(假设janoshik等人使用HPLC-MS)希望能

找到研究过这个问题的人帮我解答一下,谢谢。 🙂 I think this is very relevant to @Gr33dyOctopus’ question. Because this could make the soup that we recon a different compound. I am very interested in this because I’m in glps primarily for the less publicized benefits. Also maybe if our subcutaneous pH is not the appropriate pH to free the base, maybe it’s better to buffer the recon…

I have argued this with Jano and the other labs around in circles. They have a vested interest in telling us their RP HPLC-UV whatever test gives us all the info we need. But it doesn’t really. It probably gives us all the info we can afford, and keeps the vendors reasonable honest. I’m not convinced it’s going to confirm molecular weight and amino sequencing… among other things. No. We cannot be sure that what we are getting is the same as what EL et al are producing. I think the testing to confirm it all would be upwards of several thousand dollars IF you can find a lab capable of doing it and willing to deal B2C single test volume.
 
deleted.user.18 said:
I have argued this with Jano and the other labs around in circles. They have a vested interest in telling us their RP HPLC-UV whatever test gives us all the info we need. But it doesn’t really. It probably gives us all the info we can afford, and keeps the vendors reasonable honest. I’m not convinced it’s going to confirm molecular weight and amino sequencing… among other things. No. We cannot be sure that what we are getting is the same as what EL et al are producing. I think the testing to confirm it all would be upwards of several thousand dollars IF you can find a lab capable of doing it and willing to deal B2C single test volume.
I can see that. Arguing from most likely issues to least likely, it would imo be nice to see what residues from the actual synthesis solvents might remain, (these are washed out, and though I’m not well acquainted with the way specs are performed, why can’t they just dilute the actual product sample we provide and directly stick it in a cuvette for mass spec and see everything in the vial? That’s what we did in school decades ago. By now we certainly have software to identify peaks, and we can even tip it off as to what processes might be leaving trash behind, and then compare to a bit of EL product. And identify some known possible apecies - TFA, acetate, sodium, and so forth. We’d have to think about the pH of course. And borrow a mg from someone with meticulous technique. (I haven’t made my first purchase yet, a bit daunting with bitcoin and federal tax forms and such) This should be cheap to do.

I still have not seen assurance that we are buying the base from anyone. (Which could entirely be my own rather major ignorance, admittedly, someone please put me out of my misery!). Anyone with an academic chemistry connection?
 
deleted.user.18 said:
If you are a member and have sufficient privileges this is the thread: https://chat.peppys.org/t/peptide-quality/42997/23
Thank you!!!! Got my invite. What does it take to get privileges? I’ve just put a lot of time into getting privileges here to post in a few places 🤣, (probably the mods are tired of seeing my same themes already, but I’m happy to have gotten some awesome conversation already). Anyway this is all slow going. (Not complaining, it all makes sense, our world constantly reminds us why we can’t have nice things.)
 
Labcat said:
I can see that. Arguing from most likely issues to least likely, it would imo be nice to see what residues from the actual synthesis solvents might remain, (these are washed out, and though I’m not well acquainted with the way specs are performed, why can’t they just dilute the actual product sample we provide and directly stick it in a cuvette for mass spec and see everything in the vial? That’s what we did in school decades ago. By now we certainly have software to identify peaks, and we can even tip it off as to what processes might be leaving trash behind, and then compare to a bit of EL product. And identify some known possible apecies - TFA, acetate, sodium, and so forth. We’d have to think about the pH of course. And borrow a mg from someone with meticulous technique. (I haven’t made my first purchase yet, a bit daunting with bitcoin and federal tax forms and such) This should be cheap to do.

I still have not seen assurance that we are buying the base from anyone. (Which could entirely be my own rather major ignorance, admittedly, someone please put me out of my misery!). Anyone with an academic chemistry connection?
As long as you don't sell crypto for fiat currency I don't think you create a taxable event. Like, buy crypto, spend it, -poof- gone. it's when you buy it and then sell it you create a capital gain or loss, and they're MOSTLY interested in your gains. But what do I know, I've only been studying taxes my whole life...
 
deleted.user.18 said:
As long as you don't sell crypto for fiat currency I don't think you create a taxable event. Like, buy crypto, spend it, -poof- gone. it's when you buy it and then sell it you create a capital gain or loss, and they're MOSTLY interested in your gains. But what do I know, I've only been studying taxes my whole life...
Well of it’s your actual WHOLE life 🤣.

So spending and seeking is different?

And if i have any left over that I didn’t spend due to some counting error, (like wise is always gonna have that leftover lol)… is that of interest to the tax people who only tax us stupid wage earners?

Anything else I need to know, sir?

Really, thank you so much for this advice. Too.
 
Labcat said:
Well of it’s your actual WHOLE life 🤣.

So spending and seeking is different?

And if i have any left over that I didn’t spend due to some counting error, (like wise is always gonna have that leftover lol)… is that of interest to the tax people who only tax us stupid wage earners?

Anything else I need to know, sir?

Really, thank you so much for this advice. Too.
I don't think having it left over is a problem. Just leave it in the wallet. You aren't paying me for advice however, and it's worth every penny you spent on it.... I'm a tax guy... but I'm not YOUR tax guy!
 
deleted.user.18 said:
I don't think having it left over is a problem. Just leave it in the wallet. You aren't paying me for advice however, and it's worth every penny you spent on it.... I'm a tax guy... but I'm not YOUR tax guy!
And I’m a biologist, but not your biologist! 🙂 . (Though I could be, we don’t really seem to carry legal risk from that. Shh don’t tell the lawyers.)

You’re still a thousand times more accurate than any google or AI. search. Thank you, for the general wisdom that is not advice! I didn’t even know about it.

I don’t have a tax guy, alas, he’d have to work for a share of debt 😜. Or medical issues, i got a lot of that too.
 
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