i am proforming a assay of material having three to four polymorphs , i have identified the polymorphs .
so while doing assay i am taking std as a one form material and my anlysing material(sample) has different forms so is this can affect the assay value .
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By Will on Tuesday, May 7, 2002 - 04:22 am:
I'm not sure if there is a question here, but I
think you are asking whether different
polymorphs will behave differently in LC.
Bearing in mind that LC all happens with the
compounds in solution, my feeling is no.
However, someone with experience may tell
us otherwise.
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By Uwe Neue on Tuesday, May 7, 2002 - 03:51 pm:
I am not familiar with the term "polymorph". What is it?
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By Will on Wednesday, May 8, 2002 - 02:14 am:
Crystalline solids tend to have several
possible lattice structures, plus solvate and
hydrate forms (polymorphs). These all have
different lattice energies and therefore the
conditions during crystallisation determine
which polymorph forms. The most stable
form does not allways form directly and
sometimes polymorphic conversions occur
during storage, exposute to moisture,
changes in temperature etc, etc.
For example, I sometimes see a polymorphic
interconversion just before a solid melts
during a melting point determination, the solid
may change from rhombic to needle like
crystals briefly.
The trouble for the drug industry is that each of
a compound's polymorphs will have a different
bioavailabilitiy. This means that the ease of
interconversion and biological properties have
to be studied for each form.
For example, a drug may be produced to be
given at a particular doseage, but on storage
in a humid environment may become a
hydrated form with lower bioavailability and
become ineffective at the prescribed dosage.
Or even worse, a drug produced as a solvate
might, over time, convert to a non-solvated
form, possibly with higher bioavailability.
Dosing at the prescribed levels may result in a
dangerous amount of the substance being
administered.
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By Uwe Neue on Wednesday, May 8, 2002 - 06:44 pm:
Based on the information on polymorphs, I completely agree with Will's statement. There is no chemical difference, and you are analysing things in solution. Therefore all polymorphs should give identical results... Well, maybe with the exception of different forms of hydration, or solvation, for that matter. But you should be able to determine by other means, if this is the problem.
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By Anonymous on Monday, May 13, 2002 - 05:58 am:
but my sepcific observation is like this
that my compound havign three forms identified
LETS SAY A , B , AND C
NOW I HAVE ONLY ONE STD WHICH IS CHARACTERISED AND STANDARDISED HAVING FORM C
NOW WHEN I AM ASSAYING B FORMS SAMPLE I AM GETTING ASSAY VALUE HIGHR MORE THAN 100% ITS AROUND 103-105 . AND WHEN I AM ASSAYING A I AM GETING OKEY VALUE . JUST NOW WE CAME TO KNOW THAT THERE IS ONE MORE FORM STIL THAT IS D SO I STARTED ASSAYING D AND I GOT LESS ASSAY VALUE THEN EXPECTED THAT MEANS LESS THEN 95% SO IS THIS ALL THE POLYMORPHS PROBLEAMS .
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By Anonymous on Monday, May 13, 2002 - 02:32 pm:
Polymorphs are just different crystalline structures of a solid material. When you dissolve them, you loose all crystalline structure, i.e. you can't have polymorphs in solution. Only a solvated molecule. To analyze polymorphs, you need a spectroscopist. You may be able to correlate spectroscopic data to DSC.
For anonymous on May 13 above. What is the purity of your standard? Just because it's labeled 100% "form C" does not mean it's 100% pure. A number of factors go into a purity determination for a ref. std.
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By Tom Mizukami on Monday, May 13, 2002 - 07:00 pm:
"NOW WHEN I AM ASSAYING B FORMS SAMPLE I AM GETTING ASSAY VALUE HIGHR MORE THAN 100% ..."
My guess is that your polymorphs have different amount of associated water - monohydrate vs trihydrate etc. or perhaps one ploymorph is more hygroscopic than another. Have you done KF and measured the amount of free water in your different polymorphs? Perhaps a moisture adjustment to your standard weights is all you need.
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