Extracting Or Separating These Substances
A thorough knowledge of the physical properties of the compounds in the medication that you are dealing with must be known. The Merck Index will have these substances listed along with their mp, bp, and solubilities. The best way to show you how this separation is effected is to give you some examples.
Let's say that I just purchased 6 fl. oz. of average codeine cough syrup. I read the label and find that every fl. oz. contains:
Acetaminophen 1000 mg times 6 = 6000
Pseudoephedrine 60 mg times 6 = 360 mg
Codeine sulfate 30 mg times 6 = 180 mg
Dextromethorphan 30 mg times 6 = 180 mg
Obviously there is quite a bit of dope in these cough medications. Remember to multiply, the amount per dose times the total fluid oz. of the bottle, when figuring the total amount available. Now, I look up the properties of each and record each. Consider what form I'm dealing with; a liquid. How do we separate liquids? Column chromatography would work great. Read the section on column chromatography carefully. Then refer to the properties that you just recorded.
From what we see on the next page (properties) we can tell that codeine is not very soluble, so it stands to reason that this will be the last substance that will be eluted from the column. Acetaminophen looks the most soluble, so lets get rid of it first. Acetone looks like a good choice, but its hard to tell because the Merck Index did not say if the other substances are soluble or insoluble in acetone. Try a little and see what types of crystals appear upon evaporating off the solvent, test the melting point and see if it is exactly as stated for acetaminophen. If there are only two types of crystals then it may be easier to go ahead and elute these and then separate them from each other later. Also, if you get two or more compounds that give much of the same effect, then there is really no point in separating them (e.g. acetaminophen and codeine), unless you plan to modify one of the compounds, then it must be done.
Soluble In Hot Water
Not Soluble In Cold Water
Codeine sulfate (note the substances which are incompatible with codeine)
Hydrobromide ethanol methanol acetone ethyl acetate water (cold & hot)
30 ml of water per g 1 !/4 L of ethanol per g chloroform propylene glycol hot ethanol petroleum ether benzene pentane chloroform chloroform ether, ethyl ether, ethyl
Next, we see that Dextromethorphan is soluble in chloroform and the remaining two substances are not. Add only enough chloroform to get the calculated amount of substance.
It takes a lot of ethanol to elute 1 g of codeine. A little ethanol elutes a lot of pseudoephedrine, so we use just enough cold ethanol to remove the pseudoephedrine (the colder the ethanol the better we keep the codeine from mixing in). If the ephedrine is to be reduced it must be purified completely.
If chromatography scares you, then the substances can be distilled out (sometimes, not always). If distilling, it is nice to know the boiling points, so you will have a good idea of when the substance is coming over. If you cannot find the bp then you will have to watch the temperature given on your thermometer very closely, when it changes, then the substance that is coming over is changing (see the distillation section of the equipment chapter). I prefer to distill off the inert crap and run the residue through the chromatography column, or visa versa. Always use a high vacuo during the distillation and never over-heat (when things stop coming over, stop the heat). Many of the substances are decomposed by too much heat. A vacuum helps, but you should look at the melting points and boiling points to keep from ruining the product.
Let's try separating some solid form of OTC (over the counter) drugs. The most common is the decongestant, allergy, cold relief tablets. Rule #1 is try to find the tablets that do not have coloring to them, the plain white pressed tabs such as Tedral are perfect.
For an example Tedral contains:
1. Theophylline. 130 mg per tablet, it is useless for a recreational drug so it must go. Note: Always record mp and other properties.
Soluble In Not Soluble In
120 ml H20 dissolves 1 g ether, ethyl
80 ml ethanol dissolves 1 g 110 ml chloroform dissolves 1 g
2. Phenobarbital. This is put into Tedral to counteract the sympathomimetic effects of the ephedrine. it is a good sedative once separated from the ephedrine.
Soluble In Not Soluble In
1 g dissolves in 1 L of water none listed
1 g dissolves in 700 ml benzene 1 g dissolves in 40 ml chloroform 1 g dissolves in 1 L ether
3. Ephedrine. There are different types of ephedrine, so it may be necessary to experiment and find the one you are trying to extract, but they are generally the same, so most solvents may be good enough to get some product to test.
Soluble In Not Soluble In
1 g dissolves in 4 ml water ether, ethyl
1 g dissolves in 40 ml ethanol
All three of the substances above are soluble in chloroform (chloroform evaporates fast, too), so to begin with I would dissolve the tablets by refluxing in chloroform for 10 minutes. Filter off the inert matter from all three of the substances by utilizing hot filtration. Now run the residue through the chromatography column after evaporating off the chloroform. The column is the most efficient method, but it is not completely necessary. Let's say that we are not using the column.
Ephedrine is very soluble in water, so using cold water (almost freezing) we will remove the ephedrine (remember that 4 ml dissolves 1 g of ephedrine so use a very small excess of water).
To get rid of the theophylline from the useful phenobarbital; dissolve the phenobarbital with ether. This will take a large amount of ether, but do not use too much. Heating slightly may reduce the amount of ether. Also, cheaper and less suspicious solvents may replace the ether, only experimentation will tell.
I will now go into the extraction of adrenalin. I felt this necessary as it can be extracted from certain glands of most mammals. This drug should be legal most everywhere and can be synthesized. Also, see Ber, 37, 4149 (1904) or British pat. 816, 857 (1959).
The adrenal medulla secretes only one hormone and that is epinephrine (adrenalin). This is probably why the fresh gland contains such a surprisingly high concentration of the hormone (0.2%). To retrieve the adrenalin; acquire both the medulla and cortex glands. Most any butcher will go through the trouble of removing these for a small fee, if you can get someone at a large slaughter house to do this for you, then the reward will be a very large quantity of adrenalin.
Finely chop the glands with a razor blade or pulverize in a blender. Extract the adrenalin into a small excess of hot H20 concentrate in a vacuum. Remove the salts and proteins (if proteins are not removed, they will give the same effect as blood poisoning from a rattle snake bite, but worse) by precipitating with alcohol and remove this precipitate by filtration. The filtrate is then distilled in vacuo to remove the adrenalin (I would perform the filtration above, at room temp). Add a little ammonia to precipitate the active compound and filter from the water. The amount of ammonia depends on the amount of substance. To experiment, to get the proper amount, add a very little amount of ammonia to the distillate and filter off any precipitate if any forms. Add a little more ammonia and filter. Repeat until no more precipitate is formed, remember the amount of ammonia used and use this amount on the same amount of filtrate during the extraction of the next batch.
The combined precipitate must be purified by dissolving in acid (hydrochloric or sulfuric will do), precipitate the impurities by adding alcohol and filter them off. Distill off the alcohol and precipitate the adrenalin by adding ammonia as before. This process is repeated until the 211212° mp is achieved, and the product is a clear crystalline, free of ash.
Adrenalin is rapidly destroyed by the enzyme amino-oxadize and is therefore ineffective orally. It may be injected, snorted or possibly dissolved under the tongue. It is of considerable value to restore heart beat after sudden heart failure. This is due to its powerful stimulating effect.
This is enough to give you the general procedures to extract any of the over the counter drugs that you may run into. If you are still hopelessly confused, then you really are not educated enough in the chemistry field to be working in a laboratory.
Note: Synthetic adrenalin can be emptied into a vessel, from those Primatine Mist type inhalers that asthma attacks are treated with, and extracted and precipitated (water and ammonia respectively) as described above.
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