Answer ALL parts of this question
Problem 1:
(a) Suggest a typical 2D NMR experiment that can be used for the elucidation of drug protein interactions. Critically appraise the fundamentals of this technique and with the aid of an example, highlight how results can be monitored.
(b) You have been provided with a sample that contains a counterfeit mixture of drugs. Critically describe, with aid of a figure, an NMR experiment that can be used to separate and identify the components in this mixture.
Problem 2: Answer ALL parts of this question
(a) Propose an experimental method, using a triple-quadrupole mass spectrometer, for the identification of an unknown drug metabolite observed during phase I clinical testing.
Your answer should include:
(i) Consideration of different ionisation methods, and the mass spectrometric information generated by them.
(ii) Discussion of the different mass spectrometric scanning modes available, and the information each scanning mode can provide.
(iii) Discussion of the use and limitations of gas chromatography and liquid chromatography as separation methods that supplement mass spectrometry for use with complex analyte matrices.
(b) For the low-resolution electrospray ionisation of the non-steroidal anti-inflammatory drug diclofenac (C14H11Cl2NO2), predict the pseudo-molecular parent ion mass spectrum and isotope distribution, including mass-to-charge ratios of expected peaks, and the calculated relative abundances of any isotope peaks.
Problem 3: Answer ALL parts of this question
The following questions are related to chiral separations:
(a) Discuss why pharmaceutical companies care about the chiral purity of their compounds.
(b) Discuss how racemic mixtures are separated.
(c) If you must validate a specific chromatographic methodology, discuss how you evaluate the key validation parameters.