Sciencemadness Discussion Board

Will glacial acetic acid esterify testosterone?

bmays - 3-10-2014 at 21:35

"Heptanoic acid is used to esterify steroids in the preparation of drugs such as testosterone enanthate, trenbolone enanthate, drostanolone enanthate and methenolone enanthate (Primobolan)." - wiki

What would be your guess, and if you could briefly explain why that would be great. I will research more, i just don't know where to look in my organic chemistry book. It is very old also so maybe i need a knew one anyway. thanks

CuReUS - 3-10-2014 at 23:20

glacial acetic acid is a much stronger acid than heptanoic acid(because of +I effect of six carbons on the carboxylic carbon in heptanoic acid,so that after it becomes R-COO- from R-COOH ,the negative charge formed is not delocalised and but increased which makes it unstable) and as esterification reactions need acidic conditions,i think glacial acetic acid can esterify testosterone

but heptanoic acid may be used for esterifying for other reasons.
possibly such a long chain is added so that the drug takes more time to be metabolised by the liver and also less drug is released into the blood stream(due to the first pass effect) so that a sudden rise in blood testosterone level does not occur which might cause a heart attack-see testosterone wiki under "adverse effects"

initially i thought that esterifying it with heptanoic acid would make it more fat soluble so that it can be easily taken up by the genital tissues and other lipid rich organs but testosterone is already a water insoluble hydrophobic molecule(as it belongs to the cholestrol family) so i dont think that is the reason

but in the same testosterone wiki page if you look at the right hand table under the structure of testosterone,under " Pharmacokinetic data",it says that 90% is excreted by the urine,also the authorities at all sports competitions check for doping by an urine test to find the testosterone/epitestosterone ratio in the urine .

for testo to be excreted by urine,it must be water soluble(you could say that it might have been converted to some soluble compound by the liver but in the dope test they measure ratio of testo/epi testo,not some other compound(epi testo is just a stereoisomer of testo),so this is a mystery:o

interesting question indeed :cool:

info on testosterone

first pass effect

PS: you could read biochemistry books for info on natural products

such as biochemistryleningers principal of biochemistry

or


principals of biochemistry by donald voet


[Edited on 4-10-2014 by CuReUS]

Chemosynthesis - 4-10-2014 at 17:33

Can you perform an internet search instead of asking all these simple questions? Look at the structure for "testosterone acetate" and see if that answers your question. I found your recrystallization information from public domain sources, so you could too. There are many other resources available online than just wikipedia. This isn't a personal pharmchem resource. If you don't know how to use an organic textbook yet, I recommend searching by reaction type (esterification) or functional group (reaction of alcohol/ester). It is not difficult.

As an aside for the above, esterification is usually not a strategy to adjust pharmacokinetic metabolism due to plasma esterase prevalence in systemic circulation; rather, it is to adjust the partition coefficient. The compartmentalization of a more lipophilic drug into fat tissues acts to slow systemic distribution and increase the half-life, similar to your first suspicion, but more related to the route of administration (IM injection) than the tissue targeting. Lipophilicity in terms of targeting is more common for blood-brain barrier penetrating (I.e. morphine to heroin) or intestinal absorption.

If you look at the JAMA article cited on the wikipedia page, the stage IV post marketing surveillance Kaplan-Meier makes it clear, in accordance with the currently hypothesized etiology of 5-beta-epimer induced downstream polycythemic viscosity, or angiotensinogen synthesis increases, that acute cardiotoxicity is a statistical non issue.

Furthermore, excretion is not necessarily unchanged excretion. Most administered testosterone becomes albumin or hormone protein bound, which prevents utilization by target tissues and their metabolic pathways. Testosterone is very lipophilic, and thus is biotransformed into a more polar molecule for excretion. In this case, the main biotransformation is phase II conjugation for urinary excretion, which is opposed to fecal excretion or other metabolic reactions. It is very easy to test for a conjugated hormone, and most serious drug tests are GC-MS. This will absolutely detect a glucuronidated or sulfated testosterone metabolite, and can then be further confirmed via carbon isotope testing.

CuReUS - 5-10-2014 at 05:04

Quote: Originally posted by Chemosynthesis  


rather, it is to adjust the partition coefficient.

i thought about partition coefficeint but then i thought that it just means the same as the ability of a particular substance to dissolve in two different solvents i.e lipophilic or lipophobic ,so i didnt mention it.
Quote:
The compartmentalization of a more lipophilic drug into fat tissues acts to slow systemic distribution and increase the half-life, similar to your first suspicion, but more related to the route of administration (IM injection) than the tissue targeting
so you mean that it is made more lipophilic so that it can be easily absorbed when it is injected intra-muscularly instead of forming a blister(kind of like a "heroin blister" in smack addicts;))
Quote:
Furthermore, excretion is not necessarily unchanged excretion...... Testosterone is very lipophilic, and thus is biotransformed into a more polar molecule for excretion. In this case, the main biotransformation is phase II conjugation for urinary excretion.... It is very easy to test for a conjugated hormone, and most serious drug tests are GC-MS. This will absolutely detect a glucuronidated or sulfated testosterone metabolite, and can then be further confirmed via carbon isotope testing.

so that means that although the wiki page says that they test for testo/epitesto ratio ,they actually test for a conjugated or sulphated testo molecule.

P.S -i hope you dont mind me asking,but are you a doctor or a pharmacist because you are a freakin genius:D

Chemosynthesis - 5-10-2014 at 06:01

Quote:
Quote:
Quote: Originally posted by CuReUS  

i thought about partition coefficeint but then i thought that it just means the same as the ability of a particular substance to dissolve in two different solvents i.e lipophilic or lipophobic ,so i didnt mention it.

In essence, yes. It's often used as a physico-chemical descriptor to describe where unbound drug partitions in the body in the absence of transport proteins, metabolism, ionization, etc.
Quote: Originally posted by CuReUS  
so you mean that it is made more lipophilic so that it can be easily absorbed when it is injected intra-muscularly instead of forming a blister(kind of like a "heroin blister" in smack addicts;))

That is a result. It's primarily for tailoring the rate of distribution from the muscle into the bloodstream, which is proportional in many drugs to the ester length (greater lipophilicity, lower hydrophilicity).
Some very polar salts are injected IM, but I believe the location and vascularization of tissue are the most important factors there. Sterility, pH, depth of injection, ease of immune cell access to tissue/vascularization, etc. will all have some effect on this, and can lead to the blistering effect, as well as abscess formation or Nicolau Syndrome.
Quote:
so that means that although the wiki page says that they test for testo/epitesto ratio ,they actually test for a conjugated or sulphated testo molecule.

I'm not sure how every lab does it (apparently LC-MS is getting more popular), but total testosterone can be corrected for mathematically as an addition to conjugated measures, or empirically summed with the conjugated forms. Either way, it's only an estimated 3% error if you ignored it. If you're interested, check out DOI: 10.1016/j.jpba.2009.01.027

I appreciate the compliment, but my background is complicated and I am a pretty private person.

aga - 5-10-2014 at 12:07

@Chemosynthesis
Quote:
my background is complicated and I am a pretty private person

Me too. Please elaborate in General Terms, as i'm also a really Nosey person.

'No' would also be an appropriate reply.