Synovex and Estrogen

If your goal is to dissolve all the Synovex, then your goal is to dissolve all the estradiol benzoate as well.

Yes, it would be better to leave as much EB undissolved as reasonably possible.

Absolutely, it would be desirable to have a good figure for solubility of TP in methanol. There’s no reason you’d have to consider it sacrificed – it would be completely recoverable – but your taking the trouble to determine this would be very helpful.

I’m not sure what was unclear about the procedure I described. It was simply to dissolve in minimal methanol required to dissolve all the TP, allowing sufficient time and mechanical breakup/agitation for that to occur, then pushing out as much of that nearly-saturated methanol solution as reasonably practical without forming a hard-pack that would be difficult to push anything else through, then pushing the remaining nearly-saturated methanol solution through with a methanol/water solution.

One really could just use additional methanol, but my thought was that 75/25 methanol/water would be less prone to unnecessarily dissolving additional EB in the brief time involved. Not a major point.

Now, if the 1 in 6 figure given by Sigma-Aldrich is correct and not the pharmaceutical value of 750 mg per mL, and if methanol has equal solubilizing ability, even then Synovex containing a nominal 20 g of testosterone propionate should require only 120 mL of methanol at room temperature, let alone with added heat.

So yes I do expect you’re using much more than necessary.

Incidentally, using heat would be a completely valid method for saving time with the lesser volume of methanol, rather than allowing all the time I described at room temperature. But one would cool back to room temperature before proceeding further. The TP would remain dissolved if enough methanol were used, while the excess EB that went into solution only because of moderately increased temperature (e.g. 50-60 C) would recrystallize.

Testolius, are you dissolving everything i.e. the whole pellet, or just the hormone(s)? If the figures Bill gave are correct, then just because everything hasn’t dissolved doesn’t mean the hormone(s) hasn’t dissolved. I have no experience with this procedure. I’m just throwing a guess out there from the reading I have done on this thread.

[quote]Bill Roberts wrote:
If your goal is to dissolve all the Synovex, then your goal is to dissolve all the estradiol benzoate as well.

Yes, it would be better to leave as much EB undissolved as reasonably possible.

Absolutely, it would be desirable to have a good figure for solubility of TP in methanol. There’s no reason you’d have to consider it sacrificed – it would be completely recoverable – but your taking the trouble to determine this would be very helpful.

I’m not sure what was unclear about the procedure I described. It was simply to dissolve in minimal methanol required to dissolve all the TP, allowing sufficient time and mechanical breakup/agitation for that to occur, then pushing out as much of that nearly-saturated methanol solution as reasonably practical without forming a hard-pack that would be difficult to push anything else through, then pushing the remaining nearly-saturated methanol solution through with a methanol/water solution.

One really could just use additional methanol, but my thought was that 75/25 methanol/water would be less prone to unnecessarily dissolving additional EB in the brief time involved. Not a major point.[/quote]

No, the procedure was clear, I just didn’t understand the concept. Maybe the use of the Whatman threw me - I usually simply use a coffee filter for the initial separation of dissolved test-p from undissolved estro & any binders…do you think a coffee filter is fine enough to catch undissolved estro?

I have some time this weekend and will try to get an experimental value for test-p solubility in warm methanol.

[quote]W.H.B. wrote:
Testolius, are you dissolving everything i.e. the whole pellet, or just the hormone(s)? If the figures Bill gave are correct, then just because everything hasn’t dissolved doesn’t mean the hormone(s) hasn’t dissolved. I have no experience with this procedure. I’m just throwing a guess out there from the reading I have done on this thread.[/quote]

yes, I see what you are saying. I was trying to get the entire pellet dissolved. I can see now that I was mistaken in my thinking and that there should be approx (at least) 10% undissolved solids representing the undissolved estradiol. I don’t know how to get to that level of precision using the crude methods of ‘kitchen chemistry’ but suspect the best way is to come up with a reasonably accurate solubility of test-p in methanol and then aim just to the short side of that, in effect leaving some undissolved test-p, but ensuring almost NO dissolved estradiol.

I suspect BR was right and the conventional method is using far too much methanol.

As I mentioned, I will experiment this weekend and post results here when complete.

[quote]testolius wrote:
Bill Roberts wrote:
If your goal is to dissolve all the Synovex, then your goal is to dissolve all the estradiol benzoate as well.

Yes, it would be better to leave as much EB undissolved as reasonably possible.

Absolutely, it would be desirable to have a good figure for solubility of TP in methanol. There’s no reason you’d have to consider it sacrificed – it would be completely recoverable – but your taking the trouble to determine this would be very helpful.

I’m not sure what was unclear about the procedure I described. It was simply to dissolve in minimal methanol required to dissolve all the TP, allowing sufficient time and mechanical breakup/agitation for that to occur, then pushing out as much of that nearly-saturated methanol solution as reasonably practical without forming a hard-pack that would be difficult to push anything else through, then pushing the remaining nearly-saturated methanol solution through with a methanol/water solution.

One really could just use additional methanol, but my thought was that 75/25 methanol/water would be less prone to unnecessarily dissolving additional EB in the brief time involved. Not a major point.

No, the procedure was clear, I just didn’t understand the concept. Maybe the use of the Whatman threw me - I usually simply use a coffee filter for the initial separation of dissolved test-p from undissolved estro & any binders…do you think a coffee filter is fine enough to catch undissolved estro?

I have some time this weekend and will try to get an experimental value for test-p solubility in warm methanol.[/quote]

My concern was, if the solubility of TP in methanol is really anything like as high as the pharmaceutically-given value for TP in ethanol, that if using a coffee filter it might be problematic getting the majority of the methanol out of the resulting fairly paste-like solution/mixture. Using a syringe would allow pushing more of it out, and then allows a push-through with the additional solution that would likely be more efficient than pouring such a solution onto a paste on a coffee filter, as the added solution could tend to just go around rather than through.

It would be better to have the solubility in room temperature methanol. If you are doing it with crystals, there should be no issue of slowness in dissolving at room temperature.

Your doing this will be really great information!

This afternoon I performed some solubility experiments and here are my results for solubility of testosterone proprionate in methanol:

  1. A 2g sample of test-p (derived from 4x super-saturation/selective recrystallization from Synovex H) was slowly dissolved in 20°C methanol (Heet). Although most of the crystalline powder was in solution at approx. 1g/40ml, it was not fully dissolved (crystal clear) until 1g/115ml.

  2. I completely dissolved 1g of test-p crystals in 12ml of 60°C Heet.

Comments?

Your figures are radically different than the two of the three values given in the scientific sources that I found for solubility in ethanol. (Not the same solvent, but generally it acts pretty similarly.)

A possible cause, though not necessarily so, is that even with the processing you already did, the material was in fact a mixture of some sort. If that were the case, it might be the additional substance or substances that required all the extra solvent.

Something indicating this might be the case is that if most (more than 50% of a substance) is dissolved in 50 mL, then less than 80 mL will be required to dissolve all of it. If 115 mL was required for all of it, then no more than about 1/3 of it could have been dissolved in 40 mL. Now it could be that you mistook “1/3 dissolved” for “mostly dissolved” but it’s also might be that you did not, you were quite right in your observation.

At this point the question seems unresolved for sure, but it seems to me:

A) The pharmaceutical value of ~750 mg per mL of ethanol is probably wrong. It did seem a surprisingly high figure.

B) Your findings would agree with the Sigma-Aldrich value of 10 mg/mL, which seems a surprisingly low figure, but only if your impression that most was dissolved with 40 mL was wrong.

It would be possible to find out if you in fact have a mixture, if you could repeat the process but this time dissolving in only the 40 mL, filtering, and then evaporating the solution and weighing the crystals.

If amount dissolved was in higher proportion than 1 gram in 115 mL – in other words if you recover more than about 350 mg – then you have a mixture, unfortunately.

Actually we really would want to use enough methanol such that whatever ratio of methanol/water is used would fully dissolve the testosterone propionate. So, and I should have realized this before, really the big question is how much methanol/water, in whatever ratio is used for the hydrolysis via water being added with the saturated NaOH, is needed to dissolve the testosterone propionate.

By the way, and now we are really getting into an area where commentary without having done the procedure becomes really lacking, there’s a potential major problem in doing the hydrolysis in methanol/water, particularly where the amount of water is pretty small.

If the nucleophilic attack – fancy phrase for “thing attacking the ester” – is with methoxide, as is likely in a concentrated methanol solution with little water, your immediate product is not sodium estradiol, but estradiol methyl ester. Which is not water soluble, and the whole idea is to convert the EB to water soluble form.

True, maybe sooner or later an attack will be by hydroxide and thus we actually get sodium estradiol. However if we have to wait through a large number of attacks of the wrong kind before getting one of the desired kind, that increases chance of an attack that we don’t want occuring on the TP in that time.

Two possible answers to that:

First, if the planners of this method thought they were getting sodium estradiol, for the most part they may be wrong but nonetheless methyl estradiol may be more soluble than estradiol benzoate so at least something is accomplished, though not as much as hoped, yet still maybe it is OK.

Or second, we could clean up the problem by using a non-nucleophilic solvent, for example acetonitrile/water.

But one really would have to experiment with that to say how to do it.

Getting back to the main problem, if you could repeat the experiment with the 40 mL and see how much of 1 gram does dissolve into that, it would let you know if your 1 gram is at least largely one material, or is very much a mixture.

I also thought perhaps my sample of test-p was not pure enough, but the only thing it could have been contaminated with is estradiol benzoate, which is listed as being “freely” soluble in methanol. It got me to thinking, and I will share so someone can correct me if I’m wrong…

The separation of estradiol benzoate from testosterone proprionate in Synovex H takes place in the recrystallization phase. I can now see that what I posted above in reply to W.H.B. was incorrect - we are not trying to separate by the differences in solubility (as implied by the comment about not trying to dissolve EVERYTHING lest we include the estradiol).

The procedure calls for making a supersaturated solution of a mixture of 10:1 test-p:estradiol. This can best be accomplished by dissolving the pellets in warm methanol (60C is about as close to the boiling point of methanol as is practical). Insoluble binders are filtered out. Water is then added.

(For the time being I am going to leave out anything about saponifying estradiol with sodium hydroxide. This is both to simplify and confine the discussion to selective recrystallization, and because in my experience is where the vast majority of folks run into trouble and manage to produce steaming yellow slimy glop of unknown composition…at which point they usually then post and ask if anyone knows how to salvage or if it is safe to just run through a Whatman and inject).

My understanding is that the water is fully miscible in methanol, and when added, combines with the methanol making less methanol available to hold crystals in solution. At this point, the substance that is the most supersaturated (test-p) starts to fall out of solution. As we add more water, more crystals fall out of solution, including an increasing amount of estradiol, so we want to stop before we get too much estro - this could use some fine tuning, but I don’t see how much could be done using the crude methods available to most home experimenters, leaving it the part of the procedure that is more art than science.

If you have a saturated solution of both testosterone propionate and estradiol benzoate in methanol – each being saturated if that be the case – and you add water, why would you say only testosterone propionate will crystallize out?

That would be reasonable if estradiol benzoate were more hydrophilic but I don’t think that’s the case, or not much so anyway if at all.

Where the process can work is if, though EB and TP may have been saturated in the first place, the EB is converted to a more soluble substance which is not saturated and can thus tolerate some water being added. This would be particularly true if being converted to much more hydrophilic form than testosterone propionate, such as sodium estradiol.

Seems like alot of work and expense for a widely available injectable.

Yes, that’s why I have not tried it myself, other than one failed attempt (over-hydrolyzed) about 10 years ago. That makes it impossible for me to give a method that would work for sure.

Well, other than the completely different method that I did employ successfully, but which requires a rotovap, which people don’t have.

[quote]Bill Roberts wrote:
If you have a saturated solution of both testosterone propionate and estradiol benzoate in methanol – each being saturated if that be the case – and you add water, why would you say only testosterone propionate will crystallize out?

That would be reasonable if estradiol benzoate were more hydrophilic but I don’t think that’s the case, or not much so anyway if at all.

Where the process can work is if, though EB and TP may have been saturated in the first place, the EB is converted to a more soluble substance which is not saturated and can thus tolerate some water being added. This would be particularly true if being converted to much more hydrophilic form than testosterone propionate, such as sodium estradiol.[/quote]

My understanding is that since there is 10x as much test-p, it is supersaturated but the estradiol is not, hence when water is added the test-p starts to drop out of solution first.

As far as “why all the trouble for an easily available injectable?”…maybe not so easily available for all of us…I will admit, if I had good sources these questions would not be of much interest to me.

Well I didn’t have a source till I googled “STEROIDS”

No, because the solubility ratio favoring the TP is far in excess of the ratio of TP to EB. The EB is saturated as well.

Or if you dissolve all the EB then actually the EB is at much higher percentage saturation than the TP is.

[quote]winkroar3 wrote:
Well I didn’t have a source till I googled “STEROIDS”[/quote]

And i wonder if your source is expensive and decent quality or cheap and shite quality…?

[quote]Bill Roberts wrote:
No, because the solubility ratio favoring the TP is far in excess of the ratio of TP to EB. The EB is saturated as well.

Or if you dissolve all the EB then actually the EB is at much higher percentage saturation than the TP is.[/quote]

Bill, the only conclusion that I can reasonably come to is that I really don’t know enough to be playing around with this stuff, but then again, I have never been accused of being overly prudent. The other side of the coin however, is that despite not really knowing what I am doing, I seem to regularly produce gear that gives acceptable results, so I guess even a blind squirrel occasionally finds a nut.

Anyway, thanks for sharing what you know and helping to bounce this around a bit.

I hope there was something of use.

One can get, though it probably depends on the individual as to whether it’s acceptable, acceptable results from simply dissolving straight into oil without any of the methanol/hydrolysis/crystallization procedure, though for sure there is some estradiol benzoate dissolved. Maybe 1%, maybe half a percent… I don’t know the amount. Anyway the point is that acceptable results doesn’t necessarily mean the estradiol benzoate was removed past its natural tendency to dissolve much less anyway.

But if it works satisfactorily for you, that is what counts.

It is always difficult the first times until you get it down pat. Then it becomes second nature. The effort is worth the trouble once it the bugs are ironed out…

Actually Brook, my gear is a combination of UG and Human grade and it is top notch.
I also get my switchblades, Cuban cigars, and some other stuff online. I was only trying
to make the obvious suggestion.