resorcinol
11-17-2008, 02:50 PM
opioid salts so stuff like "oxycodone HCl" and "hydrocodone bitartrate" and "morphine sulfate" is more meaningful to people.
Most opioid mu agonists, except for a few oddities like herkinorin, contain an amine group, which is an organic functional group found in may organic compounds.
The amine group acts as a base because the nitrogen in the amine aroup has a lone pair of electrons that can form a coordinate covalent bond with a proton (hydrogen ion) -- and hydrogen ions are what acids release in aqueous solution. Since this nitrogen atom in the amine group (and all amines are basically substituted ammonia, which is also a weak base for the same reason) can accept a proton from an acid by forming a coordinate covalent bond with the proton, the amine group is a lewis base (since the definition of a lewis base is a compound that has a free lone pair of electrons that can accept a proton). Each nitrogen atom, and therefore each amine group, can accept ONE proton by forming a coordinate covalent bond with that proton.
For this moment lets focus on morphine-like opioids. Most morphine-like (morphinan / phenanthrene class) opioids have only one amine group. This means that they are monobasic... they can accept one proton and only one proton from an acid. Morphine, oxycodone, and hydrocodone are all examples of morphine-like opioids that have only one amine group in their structure and are therefore monobasic.
So now lets look at morphine sulfate. Morphine is monobasic, it can only accept on proton since it has only one amine group with a lone electron pair. Sulfuric acid, however, is H2SO4 -- look at that, it has TWO hydrogens in its formula that it can give up as protons...in other words, it's DIacidic. So, when morphine freebase and sulfuric acid react with each other, the salt looks like this: each sulfate anion is bound to TWO morphine molecules! This is because two morphine molecules are needed to accept both protons of sulfuric acid!
morphine sulfate
http://img148.imageshack.us/img148/8931/morphinesulfateqo9.jpg
So it's formula is (morphine-H+)2SO4
Oxycodone is, like morphine, monobasic. However, unlike morphine, which is almost always delivered as the sulfate, oxycodone is delivered as the hydrochloride salt. Hydrochloric acid is HCl -- as you can see, it is monoacidic, it can only give up one proton. So each chloride ion is bound to just one oxycodone cation: it's a simple one to one ratio since they're both mono(basic/acidic).
oxycodone hydrochloride
http://img148.imageshack.us/img148/4230/oxycodonehclyk4.jpg
Hydrocodone is monobasic just like oxycodone and morphine since it only contains one amine group that acts as a lewis base. Tartaric acid, however, is diacidic like sulfuric acid. So you would think we'd have a similar situation as with morphine sulfate. However, the pharma companies don't distribute hydrocodone tartrate... they deliver hydrocodone BItartrate. What this means is that they only partially neutralize the acid (tartaric acid) with the base (hydrocodone) -- they only make it give up one of its protons and not both. That's what "bi" typically means in the naming of salts. Since they only partially neutralize tartaric acid with the basic hydrocodone, and only make it give up one of its protons... it behaves like a monoacid, and we get a one to one ratio like with oxycodone HCl.
hydrocodone bitartrate
http://img148.imageshack.us/img148/44/hydrocodonebitartrateyu1.jpg
Notice that tartaric acid has only given up one of its protons, not both, hence this being the bitartrate salt of hydrocodone, and not the tartrate salt of hydrocodone.
You know a common example of this... baking soda! Baking soda is sodium BIcarbonate. The carbonic acid, which is diacidic, is only partially neutralized with the base sodium hydroxide (sodium hydroxide is monobasic), only forced to give up one of its two protons. This gives the formula NaHCO3.
Carbonic acid is H2CO3.
Notice only one of the protons of carbonic acid was neutralized by NaOH to create NaHCO3, that's why only one sodium cation is needed.
When carbonic acid is fully neutralized by the monobasic sodium hydroxide, you get sodium carbonate, Na2CO3. Sodium carbonate is sometimes called washing soda.
Notice, both protons have been neutralized... reacted with the monobasic OH in NaOH to form water and sodium carbonate, but now we need TWO sodium cations to balance out the chemical reaction and electrical charge of the molecule.
It's easier to understand acid base chemistry of organic functional groups if you relate it to simple inorganic acid base chemistry.
Most opioid mu agonists, except for a few oddities like herkinorin, contain an amine group, which is an organic functional group found in may organic compounds.
The amine group acts as a base because the nitrogen in the amine aroup has a lone pair of electrons that can form a coordinate covalent bond with a proton (hydrogen ion) -- and hydrogen ions are what acids release in aqueous solution. Since this nitrogen atom in the amine group (and all amines are basically substituted ammonia, which is also a weak base for the same reason) can accept a proton from an acid by forming a coordinate covalent bond with the proton, the amine group is a lewis base (since the definition of a lewis base is a compound that has a free lone pair of electrons that can accept a proton). Each nitrogen atom, and therefore each amine group, can accept ONE proton by forming a coordinate covalent bond with that proton.
For this moment lets focus on morphine-like opioids. Most morphine-like (morphinan / phenanthrene class) opioids have only one amine group. This means that they are monobasic... they can accept one proton and only one proton from an acid. Morphine, oxycodone, and hydrocodone are all examples of morphine-like opioids that have only one amine group in their structure and are therefore monobasic.
So now lets look at morphine sulfate. Morphine is monobasic, it can only accept on proton since it has only one amine group with a lone electron pair. Sulfuric acid, however, is H2SO4 -- look at that, it has TWO hydrogens in its formula that it can give up as protons...in other words, it's DIacidic. So, when morphine freebase and sulfuric acid react with each other, the salt looks like this: each sulfate anion is bound to TWO morphine molecules! This is because two morphine molecules are needed to accept both protons of sulfuric acid!
morphine sulfate
http://img148.imageshack.us/img148/8931/morphinesulfateqo9.jpg
So it's formula is (morphine-H+)2SO4
Oxycodone is, like morphine, monobasic. However, unlike morphine, which is almost always delivered as the sulfate, oxycodone is delivered as the hydrochloride salt. Hydrochloric acid is HCl -- as you can see, it is monoacidic, it can only give up one proton. So each chloride ion is bound to just one oxycodone cation: it's a simple one to one ratio since they're both mono(basic/acidic).
oxycodone hydrochloride
http://img148.imageshack.us/img148/4230/oxycodonehclyk4.jpg
Hydrocodone is monobasic just like oxycodone and morphine since it only contains one amine group that acts as a lewis base. Tartaric acid, however, is diacidic like sulfuric acid. So you would think we'd have a similar situation as with morphine sulfate. However, the pharma companies don't distribute hydrocodone tartrate... they deliver hydrocodone BItartrate. What this means is that they only partially neutralize the acid (tartaric acid) with the base (hydrocodone) -- they only make it give up one of its protons and not both. That's what "bi" typically means in the naming of salts. Since they only partially neutralize tartaric acid with the basic hydrocodone, and only make it give up one of its protons... it behaves like a monoacid, and we get a one to one ratio like with oxycodone HCl.
hydrocodone bitartrate
http://img148.imageshack.us/img148/44/hydrocodonebitartrateyu1.jpg
Notice that tartaric acid has only given up one of its protons, not both, hence this being the bitartrate salt of hydrocodone, and not the tartrate salt of hydrocodone.
You know a common example of this... baking soda! Baking soda is sodium BIcarbonate. The carbonic acid, which is diacidic, is only partially neutralized with the base sodium hydroxide (sodium hydroxide is monobasic), only forced to give up one of its two protons. This gives the formula NaHCO3.
Carbonic acid is H2CO3.
Notice only one of the protons of carbonic acid was neutralized by NaOH to create NaHCO3, that's why only one sodium cation is needed.
When carbonic acid is fully neutralized by the monobasic sodium hydroxide, you get sodium carbonate, Na2CO3. Sodium carbonate is sometimes called washing soda.
Notice, both protons have been neutralized... reacted with the monobasic OH in NaOH to form water and sodium carbonate, but now we need TWO sodium cations to balance out the chemical reaction and electrical charge of the molecule.
It's easier to understand acid base chemistry of organic functional groups if you relate it to simple inorganic acid base chemistry.