Re: ORGLIST: Analysis of chirality

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From: Richard Prankerd (richard.prankerd$##$vcp.monash.edu.au)
Date: Tue Jun 05 2001 - 18:38:15 EDT


Vijay, Joao and readers:

This question is one that I examined in several papers in the mid 1990s. The
approach developed avoids the use of chiral columns (either GLC or HPLC)
altogether, but it does require use of a differential scanning calorimeter.
While this is an expensive piece of equipment, it is possible that access may
be gained through a Chemistry dept. or possibly a Pharmacy or Pharmaceutical
Chemistry dept.

Basically, the method involves solid state purity analysis by detailed
analysis of the melting curve of the solid. This is a standard technique in
differential scanning calorimetry, but we were the first to apply it to this
question. Our contribution was to point out a means of unravelling the
melting curve, which consisted of multiple thermal events. We were able to
detect as little as 1% of the R isomer in the presence of 99% of its S isomer
or vice versa. The main limitation of the method is that the compound must
melt without decomposition (or at least with very little). The sample must be
purified from any starting materials, e.g., by column chromatography. The
method also fails in the unlikely event that the two enantiomers form a
racemic solid solution.

The approach is detailed in a series of three papers:

22. Elsabee, M. and PRANKERD, R.J. Solid state properties of drugs. Part II.
Peak shape analysis and deconvolution of overlapping endotherms in
differential scanning calorimetry of chiral mixtures. Int J Pharm, 86,
211-219, 1992.
23. Elsabee, M. and PRANKERD, R.J. Solid state properties of drugs. Part III.
Differential scanning calorimetry of drugs existing as racemic solid
solutions, racemic mixtures and racemic compounds. Int J Pharm, 86, 221-230,
1992.
24. PRANKERD, R.J. and Elsabee, M. Thermal analysis of chiral drugs. The DSC
behaviour of mixtures of ephedrine HCl and pseudoephedrine HCl enantiomers.
Thermochimica Acta, 248, 147-160 1995.*

The third paper demonstrates extension of the method from enantiomers to
diastereomers.

If your correspondent or other readers wish to consider this as a method for
determination of the enantiomeric excess, please contact me for further
details. As I have ready access to a suitable calorimeter, I may be able to
offer some assistance to establish preliminary feasibility of the method.

Regards
Richard

"J.Aires de Sousa" wrote:

> Date: Tue, 05 Jun 2001 10:02:54
> From: "Vijay Sane" <vsane$##$hotmail.com>
> Subject: Analysis of chirality
>
> Dear All,
> One of my colleague in India is doing his doctoral work on introduction
> of
> chirality while reducing aromatic ketones. He has a problem of
> determination
> of ee% in the compounds formed on reduction of the aromatic ketones. The
> cost of chiral GLC columns for the above analysis is quite high, US $500
> upwards, which he is unable to afford.
>
> Does anyone know of alternative methods of knowing ee % at low
> conversions(
> where purity of the products formed is low, about 30-35 % and rest is
> starting ketone ) or can anyone inform me where such columns are
> available
> but at very cheap rate or sponsor for the column?
>
> Thanking you all on his behalf
> Vijay Sane
> vsane$##$hotmail.com
> Mumbai
> INDIA
>

--
Richard J. Prankerd, PhD
Senior Lecturer
Victorian College of Pharmacy, Monash University
381 Royal Pde., Parkville VIC 3052

Phone: INT+613-9903-9003
Phax: INT+613-9903-9583

Drugs need to be designed with delivery components in mind - Takeru Higuchi





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