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Author Topic: Extraction of ergotamine tartrate from tablets  (Read 149 times)

akcom

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Extraction of ergotamine tartrate from tablets
« on: February 14, 2013, 03:36:24 AM »
Hello all, I'm in need of some advice.  How would you guys go about extracting ergotamine tartrate from pills containing no other alkaloids, only inactive ingredients.  The pertinent ones are Polyvinylpyrrolidone, Microcrystalline Cellulose, Saccharin Sodium, Magnesium Stearate and a couple organic dyes.

Any help would be much appreciated!

Edit: Perhaps I should include some more info as a starting point.  My idea would be to remove all nonpolar compounds by grinding the pills and washing with petroleum ether or hexanes.  I would then extract the residue with 7:3 acetone/H2O.  Rotovap to reduce, basify with Na2CO3, extract with ethyl acetate, and dry over Na2SO4

edit edit: my main concern here is affecting an isomerization at C8
« Last Edit: February 14, 2013, 03:58:39 AM by akcom »

newbiechem

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Re: Extraction of ergotamine tartrate from tablets
« Reply #1 on: February 14, 2013, 03:45:14 AM »
doesnt chloroform dissolve the ergotamine tartrate? i know someone who tryed this acctually and failed, but he was trying with cafeine/ergotamine pills....

i belive ergotamine is slowly despearing from the drug stores.... buy much as yo can hehehe!!   also some countrys have ergotamine in liquid form, which should be easier no?


could Dyhydroergotamine, be use for the purpose?

akcom

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Re: Extraction of ergotamine tartrate from tablets
« Reply #2 on: February 14, 2013, 03:55:25 AM »
The problem is chloroform will probably also dissolve the organic dyes.  I don't know of any countries that provide ergotamine in liquid form, but the only references I have are USA.  And no, dihydroergotamine cannot be used.

lugh

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Re: Extraction of ergotamine tartrate from tablets
« Reply #3 on: February 14, 2013, 03:58:42 AM »
The Merck Monograph:

Monograph Number:  3696
Title:  Ergotamine
CAS Registry Number:  113-15-5
CAS Name:  (5¢a)-12¢-Hydroxy-2¢-methyl-(phenylmethyl)ergotaman-3¢,6¢,18-trione
Molecular Formula:  C33H35N5O5
Molecular Weight:  581.66.
Percent Composition:  C 68.14%, H 6.06%, N 12.04%, O 13.75%
Literature References:  Vasoconstrictor found in ergot of Central Europe.  Extraction procedure:  Stoll, Helv. Chim. Acta 28, 1283 (1945).  Pharmacology:  E. Rothlin, Schweiz. Med. Wochenschrift 76, 1254 (1946).  Structure:  Stoll et al., ibid. 34, 1544 (1951).  Total synthesis:  Hofmann et al., Experientia 17, 206 (1961).  Stereochemistry:  Hofmann et al., ibid. 46, 2306 (1963).  Comprehensive description:  B. Kreilgard, Anal. Profiles Drug Subs. 6, 113-159 (1977).  LC determn in tablets:  U. R. Cieri, J. Assoc. Off. Anal. Chem. 70, 538 (1987); GC/MS determn in plasma:  N. Feng et al., J. Chromatog. 575, 289 (1992).  Bioavailablity and efficacy in migraine:  V. Ala-Hurula, Headache 22, 167 (1982).  Review of clinical pharmacokinetics and treatment of headache:  V. L. Perrin, Clin. Pharmacokinet. 10, 334-352 (1985).  Review of teratogenic risk:  G. V. Raymond, Teratology 51, 344-347 (1995).
Properties:  Elongated prisms from benzene.  Very hygroscopic.  Darkens and dec on exposure to air, heat and light.  Dec 212-214°.  [a]D20 -160° (chloroform).  Sol in about 70 parts methanol, 150 parts acetone, 300 parts alcohol; freely sol in chloroform, pyridine, glacial acetic acid; moderately sol in ethyl acetate; slightly in benzene.  Almost insol in water, petr ether.  LD50 in mice, rats, rabbits (mg/kg):  62, 80, 3 i.v.; in cats:  11 s.c. (Rothlin).
Optical Rotation:  [a]D20 -160° (chloroform)
Toxicity data:  LD50 in mice, rats, rabbits (mg/kg):  62, 80, 3 i.v.; in cats:  11 s.c. (Rothlin)

Derivative Type:  Hydrochloride
Molecular Formula:  C33H35N5O5.HCl
Molecular Weight:  618.13.
Percent Composition:  C 64.12%, H 5.87%, N 11.33%, O 12.94%, Cl 5.74%
Properties:  Rectangular plates from 90% alc, mp 212° (dec).  Sol in water-alcohol mixtures; sparingly in water or alcohol.
Melting point:  mp 212° (dec)

Derivative Type:  Tartrate
CAS Registry Number:  379-79-3
Trademarks:  Ergate (Vernleigh);  Ergomar (Lotus);  Ergostat (Parke-Davis);  Ergotartrat (Rosch & Handel);  Ergoton-A (Azusa);  Gynergen (Novartis);  Lingraine (Sanofi-Winthrop)
Molecular Formula:  (C33H35N5O5)2.C4H6O6
Molecular Weight:  1313.41.
Percent Composition:  C 64.01%, H 5.83%, N 10.66%, O 19.49%
Properties:  Solvated crystals, e.g. the dimethanolate, heavy rhombic plates from methanol, mp 203° (dec).  [a]D25 -125 to -155° (c = 0.4 in chloroform).  One gram dissolves in 500 ml water or 500 ml alc.  Protect from light and heat.
Melting point:  mp 203° (dec)
Optical Rotation:  [a]D25 -125 to -155° (c = 0.4 in chloroform)

Therap-Cat:  Antimigraine.
Therap-Cat-Vet:  Tartrate has been used as an oxytocic.

The end results from the effort applied  8)
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akcom

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Re: Extraction of ergotamine tartrate from tablets
« Reply #4 on: February 14, 2013, 04:08:04 AM »
Lugh, thank you very much.

Can anyone comment on the propensity for this compound to isomerize under acidic and basic conditions?  I'd imagine heat would exacerbate this.  Under what pH range is it stable?

Can someone explain to me why Shulgin does not obtain isolysergic acid in his hydrolysis of ET?
« Last Edit: February 14, 2013, 04:11:21 AM by akcom »

lugh

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Re: Extraction of ergotamine tartrate from tablets
« Reply #5 on: February 14, 2013, 04:18:17 AM »
The articles by Alexander and Stoll are attached  :)  The end results from the effort applied  8)
« Last Edit: February 14, 2013, 04:28:40 AM by lugh »
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akcom

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Re: Extraction of ergotamine tartrate from tablets
« Reply #6 on: February 14, 2013, 04:40:04 AM »
Such a tease!
Quote
For the analysis of ergotamine tartrate tablets and suppositories containing caffeine, acetophene- tidin, barbiturates, and belladona alkaloids' it is necessary that the ergot alkaloids first be separated from the other ingredients prior to the isolation of ergotamine from ergotaminine. For this purpose, a previously published method was found to be suitable(ref),whereby ergotamine and ergotaminine are obtained together in chloroform solution isolated from the other nitrogenous bases. This chloroform solution is then passed onto the citric acid column and the analysis continued as with the simple formulations.
I can't find the paper:
Alexander, T. G., J. Assoc. Ofic. Agr. Chemists, 43, 224(1960).
Looks like the journal is long gone :\
« Last Edit: February 14, 2013, 04:48:58 AM by akcom »

lugh

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Re: Extraction of ergotamine tartrate from tablets
« Reply #7 on: February 14, 2013, 03:24:19 PM »
Quote
I can't find the paper:

Articles that haven't been digitized have to be scanned to be made available on the internet :)  The Dictionary of Organic Compounds entry for lysergic acid is attached  8)
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akcom

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Re: Extraction of ergotamine tartrate from tablets
« Reply #8 on: February 14, 2013, 07:38:53 PM »
Unfortunately my library does not have access to JAOAC before 1992 :\
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