mole and mg amounts of bases from salts and racemic salt mixes

[Adrenochrome]

Hi bl'ers
I am trying to contrast the mass and mole ratios of dextroamphetamine base to various medications
(primarily Dextrostat and Adderall)
I have a lot of questions(?), and appreciate any help or resources that would provide me with understanding how to fill in my holes(my '?')s
Also, I am assuming I have everything I am providing here correct, I do not expect anyone to check my facts, but if you see something that you know is wrong then tell me
--------
Most of the holes have been filled, but if anyone wants to check my formula and molar mass for dextroamphetamine aspartate monohydrate and for dextroamphetamine saccharate as well, I'd appreciate it because those are figures I was deriving myself, so thats where mistakes lie if any, also check anything after that too, I'd appreciate any checking, but i'm going to redo all calculations for sig figs and stuff over spring break anyway so no one needs to make it a priority or anything hahaha, i dont incurage u to waste ur time checking my calculations if they're right, if u want to spend time on this thread theres questions that are valuable to me to be answered below
Also discussion is the most important thing!!!
--------------------
Update 3/8/7:Added Lisdexamfetamine (vyvanse) calculations, more to come soon as well as cites for information
=========================================

20mg Dextrostat contains only one active ingredient:
Dextroamphetamine Sulfate 20mg

Adderall(Instant Release) contains the following active ingredients:
Dextroamphetamine Sulfate 7.5mg
Dextroamphetamine Saccharate 5.0mg
Dextroamphetamine Aspartate Monohydrate 2.5mg
Levoamphetamine Sulfate 2.5mg
Levoamphetamine Aspartate Monohydrate 2.5mg
---------------------------------------
100mg Vyvanse contains one active ingredient:
100mg Lisdexamfetamine Dimesylate
----------------------------------
[note: for information why at this point I'm only concerned about the d- not l- , a good article is Differential Effects of amphetamine isomers on dopamine release ....
http://www.springerlink.com/content/...5/fulltext.pdf
]
----------------------------------------
Some data, some of it has been analyzed myself:
Dextroamphetamine C9H13N is 135.206g/mol


Sulfuric Acid H2SO4 is 98.08g/mol
Dextroamphetamine Suflate (C9H13N)2 * H2SO4 is 368.49g/mol
One of my main questions is regarding the amount of dextroamphetamine dissolved in the drug,

Aspartic Acid C4H7NO4 is 133.10g/mol
I believe that hydrous comounds are nH2O
Dextroamphetamine asparate monohydrate is mono so I believe n = 1
H2O is 18.0153g/mol
asparate monohydrate C4H7NO4H2O is 151.115g/mol
dextroamphetamine asparate monohydrate C9H13N*C4H7NO4H2O is 286.32 g/mol

Saccharic Acid C6H10O8 is 210.139g/mol
dextroamphetamine sacchate (C9H13N)2 *C6H10O8 is 480.551 g/mol for dextroamphetamine sacchate

-----------------------------------------------
Lisdexamfetamine Dimesylate C15H25N3O*(CH4O3)2 is 455.60g/mol

Dimethanesulfonate = Dimethansulfuric Acid?? is
The forumla is CH4O3S
Lisdexamfetamine is C15H25N3O is 263.38g/mol
Dextroamphetamine C9H13N is 135.206g/mol
L-Lysine C6H14N2O2 is 146.19g/mol
I add them put L-Lysine and Dextroamphetamine together and get ~17.8 g/mol less then the the sum of all atoms atomic weights, and it is missing an H2O, so this accounts I suppose...
=======================================
I modeled a function, it uses 3 variables to return two answers:
1stVAR = the amount of grams of the salt in question
2ndVAR = the amount of grams for 1 mol of the salt in question
3rdVAR = mol ratio of dextroamphetamine(reactant) to the salt in question(product)
1stASR = mol of dextroamphetamine for the amount of grams of the salt in question
2ndASR = the amount of grams of dextroamphetamine for the amount of grams of the salt in question
Function( 1stVAR ,2ndVAR) = 1stVAR * 1mol/2ndVAR * 3rdVAR = 1stASR * 135.206g/1mol = 2ndASR

I used this function twice so far, both times for dextroamphetamine sulfate
I believe the ratio of dextroamphetamine(reactant) to dextroamphetamine sulfate(product) is a 2/1 mol ratio
The amount of grams in 1 mol of dextroamphetamine sulfate is 368.49grams
The first amount of grams I used for dextroamphetamine sulfate was 20mg or 0.020grams
The second amount of grams I used for dextroamphetamine sulfate was 7.5mg or 0.0075grams
========================================
Dextrostat 20mg
from 20mg of dextroamphetamine sulfate:
1.086 * 10^-4 mol of dextroamphetamine
.01467grams or 14mg dextroamphetamine
14mg dextroamphetamine in 20mg Dextrostat
------------------------------------
20mg = .01467mg
------ = ------
45mg = .033mg
------------------------------Dextrostat 45mg would have 33mg
20mg = .01467mg
------ = ------
40mg = .02934
------------------------------Dextrostat 40mg would have 29mg
20mg = .01467mg
------ = ------
10mg = .00733333333
-------------------------------Dextrostat 10mg would have 7.1/3mg

20mg Adderall
from 7.5mg of dextroamphetamine sulfate:
4.071 * 10^-5 mol of dextroamphetamine base
2.5mg of l-amp sulfate = 2.7525mg of l-amphetamine base (73.4% by weight)
5.0mg of d-amp saccharate = 2.8mg of d-amphetamine base (56% by weight)
2.5mg of d-amp aspartate h2o = 0.5925mg d-amp base (47% by weight)
2.5mg of l-amp aspartate h2o = 0.5925mg l-amp base (47% by weight)
total amp base = 12.24mg (8.9mg d-isomer, 3.34mg l-isomer)
8.9mg of Dextroamphetamine in 20mg of Adderall

Vyvanse 100mg
from 100mg of Lisdexamfetamine Dimesylate:
2.195 * 10^-4 mol of dextroamphetamine
.02968grams or 14mg dextroamphetamine
30mg dextroamphetamine base in 100mg Vyvanse
-----------------------------------------
100mg = .02968mg
------ = ------
70mg = .020777mg
------------------------------------21mg dextroamphetamine base in 100mg Vyvanse
================================================
-----Analysis----(based on data)
For Dextrostat
Weight of dextroamphetamine base/Weight on Brand:
14mg/20mg = %70
for 100mg

For Adderall
Weight of dextroamphetamine base/Weight on Brand:
8.9mg/20mg = %44.5
Weight of racemic amphetamine/Weight on Brand
12.24mg/20mg = %61.2
Weight of dextramphetamine/weight of racemic amphetamine Base
8.9mg/12.24mg = %72.7

For Vyvanse
Weight of dextroamphetamine base/Weight on Brand:
30mg/100mg = %30
------------------------------------------------------------
(DO BETTER CALCULATIONS AND ANYALISS DONT USE USE SIG FIGS IT MIGHT NOT REALLY BE 14MG...
WHICH IS BETTER SPANSULES OR XR?.... prob sampsules... we'll see which fits better
================================================
------Conclusions--(Based on anaylsis)
When comparing Equal doses of Dextrostat and Adderall:
Dextrostat has %25.5 more dextroamphetamine base then Adderall
Dextrostat has %8.8 more (total d-, or l-)amphetamine base then Adderall
When comparing equal doses of Dextrostat and Vyvanse
Dextrostat has 70% vs 30% from Vyvanse sooo Dextrostat has 40% more then Vyvanse
------------Adderall Conclusions
The amphetamine bases in Adderall are %72.7 dextroamphetamine
The amphetamine salts in Adderall are %75 dextroamphetamine salts



=================================
Notes work in progress--------------------
If I take 45mg of Dextrostat a day that is 33mg of dextroamphetamine base..... how much Vyvanse do I want... well 33mg hmmm... and so minus 21mg gives you 12mg to account for... hmmmmm(look at sampsule information) minus 7.333 = 4.6666
45mg Daily Dextrostat:
70mg Vyvanse
10mg Dextrostat Sampuals(Shire Or GlaxoKlineSmith Co?) / Dexedrine??
5mg Dextrostat IR
All in the morning
Now compare AUC values... hmmm should compare AUC values for Spanpsules and for Vyvanse and for XRs and for Adderall(Maybe varify this with a dopamine area under curve

Maybe add the integrals of the functions that make up all the diff drugs(or i guess just the AUC...)

Now I would really need to look at ........ possibly taking
70mg Vyvanse
5mgDextrostat
in the morning
and then After first Class(~10:00am):
10mgDexedrine Spansules

or

70mg Vyvanse
5mg Dextrostat
5mg Dexedrine Spansule
in the morning
and then at about 2pm take 5mg more Dextrostat

(I would still have to look at how much Dextroamphetamine and Lisdextroamphetamine is lost in Vyvanse, compared to how much is lost in Dextrostat)

So what I need to now gather
is Cmax.... Tmax.... AUC.... graphs.... Half Lifes.... Excreation Rates.... For:
Vyvanse 70mg
Dextrostat 5mg
Dexedrine Spansules 10mg
Or possibly Dexedrine XR
Or maybe even adderall XR??
Hmmmm possibly desoxyn in place of all dextrostat IR
------------------------------------------
and relate dopamine levels or possibly norepinephrine hmmmm..........
===============================
----Future
I will type this up so it looks better, in TeX or w/e and also save as PDF
I will also put graphs on there graphing on the X axis the amount of mg on the brand name and a different thing for the Y axis, for example the amount of dextroamphetamine base, then draw a line so that we have a graphical representation, but theres many other intersting things to define the Y axis with, I'll prob do that over spring break, next week

Note that l-amp does modulate the effects of dextroamphetamine in some ways.... in the future I will calculate and compare adderalls and dextrostats affects on different neurotransmitters for example dopamine in humans so that the Cmax and Tmax etc.. of dopamine corresponding to if Adderall or Dextrostat is used, can be analyzed outside the lab



------------------------------------
It might possibly help me to know the answer to some questions:
How can I figure out how many moles of dextroamphetamine are used for every salt ?
Is it based on the number of hydrogens in the acid?
Can we predict reactants for salts by knowing only the name of the salt, if not is there any other information that could be found that would help predict reactants?
What kind of reaction is taking place to give us these salt products?
Is it an ionic reaction? If so then what is dextroamphetamines charge? Is dextroamphetamine's charge different each time?
Is this an ionic acid base nutralization reaction?
How did the reaction to form the salt come about?
Was dextroamphetamine ( or some ion of dextroamphetamine?) mixed with an acid to form a salt, or was there strange precursors involved?

If there is any strange terminology feel free to point it out
As you provide answers and I can solve the functions for different variable sets I will edit the above information so that it is correctly displayed above.

***(I want to thank raybeez for the understanding and help, and also hussness)**

 

[hussness]

Your question is complicated by the fact that saccharic acid and aspartic acid are both polyprotic acids. Primary amines are basic and have pKas in the range of ~9-11. When placed in an acidic solution with a pH significantly lower than the pKa of the amine (i.e., pKa - pH >= 2, consult the Henderson-Hasselbalch equation for further reference), most of the nitrogens will be protonated and take on a positive formal charge. The conjugate base of the respective acid basically just hangs around, providing the negative formal charge and balances the charges. The compound formed has an ionic character, and generally has different physical properties, many of which may be desirable in drug formulations -- like higher water solubility, and different crystal structure.
You would need to consult another reference for the chemical formulas of the various amphetamine salts; possibly a pharmaceutical encyclopedia.

 

[raybeez]

Rather than trying to be a math ninja and dicking around with d-amphetamine salts/moles, why not simply utilize some of the information found on the Adderall Monograph:

5mg of Adderall contains the equivalent of 3.1mg d-amphetamine base (FW=135.206g/mol)

10mg contains 6.3mg base
20mg contains 12.5mg base
30mg contains 18.8mg base ... etc. It works out that 62.5% of the amphetamine salt weight in the pills is d-amphetamine base. You should have no trouble converting that into moles of d-amphetamine now.

To answer a few more of your questions:

d-amphetamine is uncharged, but has an amine group (NH2) which can accept a proton (H+) from an acid, become charged (NH3), and then immediately form a salt with the conjugate base (becoming neutral again).

E.g. d-amphetamine-NH2 + HCl --> d-amphetamine-NH3Cl (d-amphetamine hydrochloride) ... or ... 2x d-amphetamine-NH2 + H2SO4 --> 2x d-amphetamine-NH3SO4 (d-amphetamine sulfate, note that there's 2 molecules of dextroamphetamine base for every 1 molecule of dexamp. sulfate)

The protonation of the NH2 is not an ionic reaction, but the subsequent salt formation is an ionic reaction. These are easy to predict --> acid + base = salt

 

[Adrenochrome]

It doesn't say that it is d-amphetamine base on the adderal PDR 2006 monograph, which is the same as the one the FDA and shire have i believe
The only reference to a base on the monograph is:
"Total amphetamine base equivalence"

But thanks for the information about the reaction to form dextroamphetamine sulfate!! greatly appreciated

 

[raybeez]

It doesn't say that it is d-amphetamine base on the adderal PDR 2006 monograph, which is the same as the one the FDA and shire have i believe
The only reference to a base on the monograph is:
"Total amphetamine base equivalence"

Good point, not as straight forward as I thought. I can still answer your question though, (assuming 20mg of adderall):

7.5mg of d-amp sulfate = 5.505mg of d-amphetamine base (73.4% by weight)
2.5mg of l-amp sulfate = 2.7525mg of l-amphetamine base (73.4% by weight)
5.0mg of d-amp saccharate = 2.8mg of d-amphetamine base (56% by weight)
2.5mg of d-amp aspartate h2o = 0.5925mg d-amp base (47% by weight)
2.5mg of l-amp aspartate h2o = 0.5925mg l-amp base (47% by weight)
total amp base = 12.24mg (8.9mg d-isomer, 3.34mg l-isomer)

This is based on the knowledge that aspartate monohydrate forms salts with only 1 ion, and the prediction that saccharate forms salts with 2 ions (and the math shows this is correct as the predicted amphetamine base matches the monograph value).

cheers.

 

[Adrenochrome]

^^^^^^^^^Looook up^^^^^^^^^^^^
I updated the topic (the first post on this page) by the way, it now has an anaylsis section and a conclusion section
with some interesting conclusions, worth reading IMO (its towards the end)
################


For patent #6384020 by Shire (look on google patents, or the United States patent website for this, it's got more information then I want to retype here)
Filing date: Jul 6, 2000
Issue date: May 7, 2002
Abstract
A pharmaceutical composition comprising lactitol and one or more amphetamine salts in a rapid release formulation.
It has the following, but i just rewrote it since it is a image not a text file on there
"The table below lists the ingredients and amount for the formulation of amphetamine immediate-release blend. The blend is then compressed on a rotary tablet press to produce amphetamine immediate-release tablets, 30mg.

Ingredients--------------------------Composition %-------mg/Tablet----Amount(g)
d-amphetamine Sulfate-----------------2.45---------------7.65----------1,839-----|
d,l-amphetamine aspartate-------------2.45---------------7.65----------1,839-----|
d-amphetamine saccharate------------2.45----------------7.65----------1,839-----|
d.l-amphetamine sulfate--------------40.00----------------7.65----------1,839-----|
Lactinol----------------------------------28.94----------------90.3---------21,707-----|
Lactinol----------------------------------40.00---------------124.8---------20,000----|
Microcrystalline Cellulose--------------20.00-----------------62.4---------15,000---|
Colloidal Silicon Dioxide------------------0.26------------------0.8------------192-----|
Magnesium Stearate---------------------0.99------------------3.1--------------745---|
-----------------------------------------------------------------------------------------------------
Total------------------------------------------100-------------------312.0-----------------75,00
"
You would expect Adderall 30mg to have 7.5mg of each Amphetamine Salt(and maybe it does maybe this patent is meaningless, but I'm going to go out on a limb here and say this is what it is the actual formulation Shire uses for their instant release adderall), but it looks like they have 7.65mg of each...

So I thought amphetamine is Shire putting as much dextroamphetamine
yay for Shire more bang for the buck


I just hope they are doing the same for the Dextrostat which I buy from them,
However I dout it
because next section kindof makes me think section(read below) it's just for the Adderall IR
, but I'm not sure (I'm not sure to a higher degree of how much I'm normally not sure about)


---------------------------------------------------------------------------------------section 2:
(this doesn't have anything to do with patents website, the XR patent didn't talk about the above stuff)


Also something that Isn't as interesting but raises my brows none-the-less

On the PDR Electronic Library:

Again I had to readjust tables to write it here on bluelight, so if you want a more visual table like representation consult ur friendly PDR

The for XR and IR what each row means is what it says on the brand like "Adderal 30mg"

EACH TABLET CONTAINS:
5mg
10mg
15mg
20mg
30mg

Adderall XR
Total amphetamine base equivalence
3.1mg<--------------
6.3mg
9.4mg
12.5mg<------------
18.8mg

Adderall (Instant Release Formula)
Total amphetamine base equivalence
3.13mg<--------------
6.3mg
9.4mg
12.6mg<-------------
18.8mg
---------------------------------
Conclusions?
IF shire is doing this for Adderal Instant Release, but not for Adderall XR(the only evidence of that is the section 2, so I dont know if I want to even speculate but anyway..) then maybe they are not doing it for their Dextrostat

If I presume that they don't do this for Dextrostat then I should possibly recalculate the [weight of Dextroamphetamine Base/Weight of brand] for Adderall


Anyone one have any comments, anything to add, anything at all ?

===================
====================
Added information about pro-drug lisdexamfetamine to the topic and include information(in a very rough draft form, will fix it up when i got time)

 

[customconcern]

though it's pricier by the script, i prefer it to dexedrine, and (somewhat less strongly) prefer it even to adderall.

Hell, i gave away my coke. That says something.

 

[Adrenochrome]

After I did all these lame calculations haha, I did some more research and found out these ratios are avaliable in the pharmacological reviews of Vyvanse (lisdexamfetamine dimesylate) on the FDA's website, and also in the New River patent for lisdexamfetamine...
figures ha