Drug Analysis Flashcards
Dr Dan Rathbone
What is a raw material specification?
A list of tests and corresponding limits which the results of the tests must be within. This is often based on the pharmacopeial monographs. Manufacturers may also make their own specifications for the bulk drugs made or bought.
By what three means may impurities enter the produced drug?
Synthesis, storage, related substances.
How may impurities from synthesis enter the produced drug?
From starting materials, reagents, catalysts, solvents, or by-products. They may also enter from the processing plant; heavy metals from soldered joints and iron from steel vessels.
How may impurities enter the produced drug during storage?
From degradation products generated through hydrolysis or photolysis. As well as moisture.
In terms of impurities, what are related substances?
These are usually specific synthetic precursors, by-products and degradation products chemically related to the drug. They may have biological activity similar to that of the drug.
What do the limits of impurities depend on?
The toxicity of the products (how dangerous), the feasibility (can it be done). Pharmacopeias may explain the limits.
Describe UV analysis.
Looks at chromophores, areas of conjugation (alternating double and single bonds). Identifies functional groups and can be used to identify acids or bases.
If the chromophores of the drug and the impurities are similar then UV analysis is ruled out.
Put UV, IR, and NMR in order of greatest sensitivity to least sensitivity.
UV, IR, NMR.
Put UV, IR, and NMR into the order of greatest information to the least information.
UV, IR, NMR.
Why can UV analysis sometimes be inaccurate for organic compounds?
UV energy is similar to the bonding energy for organic compounds so can photolyse the compound.
What does a greater UV wavelength suggest?
Greater conjugation and a larger chromophore.
What characteristic of chromophores leads to it being affected by pH change?
Acid or base properties.
How does an increase in electron conjugation change the lambda max?
AN increase in conjugation leads to an increase in lambda max.
How does a decrease in electron conjugation change the lambda max?
A decrease in electron conjugation decreases lambda max.
What is Beer’s Law?
Light absorption is proportional to the concentration of absorbing species.
What is Lambert’s Law?
Light absorption is proportional to path length.
Give some sample related causes for deviation from the Beer-Lambert Law.
Overlapping contaminant, Degradation (photolysis), Fluorescence, Tautomerisation (pH effects, temperature).
Why can tautomerisation cause deviations from the Beer-Lambert Law?
Different tautomers can have different absorption. This can be pH or temperature dependent.
Give some other causes for deviation from the Beer-Lambert Law.
Stray light, non-monochromatic light sauce, mismatched cells, sensitivity, solvent absorption.
Why are calibration curves used when carrying out spectroscopy?
To establish the validity of the Beer-Lambert Law for each drug under the measurement conditions to be used under an appropriate concentration range.
Describe the instrumentation of single-beam spectrophotometers.
An intense source of UV light (deuterium or hydrogen lamp - depending on the spectrum), Prism or diffraction grating monochromator, capable of high precision. Used for absorbance determination at a fixed wavelength, not to obtain a spectrum.
Describe the instrumentation of double-beam spectrophotometers.
Similar to single-beam instrumentation. Radiation split into two beams by a rotating mirror. One beam passes through the sample. The other beam passes through the blank reference cell. The two beams are compared to give the absorbance. Suitable for fixed wavelength readings and whole spectra.
What is a photodiode array?
A series of lamps at different wavelengths which is crude but gives more info. It is used more in HPLC.
Give some pharmacopeial applications of spectrophotometry.
Assay of single drugs, assay of mixtures of drugs, colourimetric methods, tablet dissolution, limit test for impurities, assays for bulk drugs or extracts.
