Development of liquid chromatography mass spectrometry methods for the monitoring of ropivacaine, endogenous steroids and dihydroartemisinin

The thesis consists of five chapters. The first chapter is general introduction to LC-MS, separation technology and extraction methods. The second chapter describes the development of a method to measure free and bound ropivacaine in human plasma using equilibrium dialysis and HILIC chromatography coupled with a high resolution mass spectrometery. In this chapter a highly sensitive method for the determination of the free and bound portion of ropivacaine in patients undergoing knee and hip joint surgery was developed. Patient samples were provided by the Golden Jubilee Hospital, Clydebank. The method was validated according to FDA guidelines. The third chapter describes the determination of α1-glycoprotein in the plasma of patients undergoing knee and hip joint surgeries using an already established method using HPLC with a polymeric reversed phase column, thus enabling comparison of the concentration of AGP protein with the levels of bound and unbound ropivacaine. This complete set of data should allow pharmacokinetic modelling studies to be carried out. The fourth chapter covers the determination of the steroids estradiol and estrone and their hydroxyl and methoxy metabolites following a derivatization reaction for provision of improved sensitivity. The free steroids are not readily ionized by ESI mass spectrometry and the derivatization procedure produces positively charged ions in order to enhance the detection of these steroids. Different reagents were used and the best sensitivity was obtained by using 2-fluoro 1, 3-dimethylpyridinium p-toluene sulphonate as the derivatising agent. This method was applied to samples obtained from patients with pulmonary hypertension in order to evaluate the role of steroids in the progression of disease. The fifth and last chapter covers the determination of an anti-malarial drug artemether and its active metabolite DHA in human plasma using a reversed phase C18 column coupled with high resolution mass spectrometry, the samples were provided by the University of Peshawar, Pakistan.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral-pg

Grantor dc:publisher.institution

University of Strathclyde

Year dc:date.issued

2015

Author dc:creator

• Abbas, Muhammad

DOI

10.48730/3xz9-bg64

Identifier

T14138

Author Identifier

201175029

OAI identifier oai:identifier

oai:strathclyde:rb68xb856