Introduction

The scientific principles and techniques you have learned in this module are routinely applied both in the pharmaceutical industry and in the clinical setting.  Two examples are:

1. Analysis of drug formulation quality before clinical testing can take place, for example the confirmation of API identity and product purity.

2. Analysis of drug concentrations in blood for therapeutic drug monitoring (TDM) in patients, for example for a drug with a narrow therapeutic window or in cases where the patient has impaired renal clearance, which may include analysis of the drug and identification of its metabolites in patients taking part in a clinical trial. 

In this assignment, we will apply these principles to the drug aciclovir (acyclovir).

PART 1

1. Aciclovir is known to have issues with bioavailability. Discuss the scientific basis of aciclovir treatment with oral dosage forms, with reference to the following:

The issue with bioavailability

The main metabolites of aciclovir.

The issues with neurotoxicity.

Include chemical structures in your answer (guideline 250-300 words plus figures and references).(20% of marks for assignment)

PART 2

2. There are different requirements for the HPLC methods used to analyse aciclovir in a formulation vs. aciclovir in a biological sample such as serum. In this part of the assignment you will compare studies for both senarios.

a. Find a recent journal article on the quantification of aciclovir in tablet formulation using HPLC. Compare and contrast the article you found with the British Pharmacopeia method for quantification of aciclovir tablets in tabular form. Then include a paragraph (guideline 250-300 words) discussing the main disadvantages and advantages of the methods or approachescompared. Your journal article should be attached to the printed paper copy of your assignment and the method highlighted.

b. A link has been provided below to the following article, C.M. McMullin et al. 'a simple high performance liquid chromatography (HPLC) assay for aciclovir and ganciclovir in serum', Journal of Antimicrobial Chemotherapy, (1996) 38 (4); 739-740.Find a more recent journal article on the analysis of aciclovir using HPLC for serum. Compare and contrast for methods in tabular form. Then include a paragraph (guideline 250-300 words) discussing the main disadvantages and advantages of the methods or approaches compared. Your journal article should be attached to the printed paper copy of your assignment and the method highlighted.

https://www.ncbi.nlm.nih.gov/pubmed/8937970

PART 3

3. Some results for the validation of an aciclovir method are shown below, in particular for a calibration curve. Plot the calibration curve and using excel, determine the limits of detection and quantification showing all relevant graphs, data and calculations. Then, with reference to the two journal articles you selected, evaluate if the limits determined would be suitable for both formulation and serum.

HINT: Review ICH Guidelines and Excel LINEST function.