Analysis of multiple drugs in small blood specimens and meconium : applications in paediatric toxicology
This thesis deals with the quantitative analysis of multiple drugs in the neonate, in blood and in meconium as an alternative biological specimen in forensic toxicology and is also concerned with the dangers of transmission of drugs used and abused by the mother to the foetus and neonate. The aims of the work were to investigate methods for performing a full drug screen on small amounts of biological specimen and to carry out a survey of illicit drug use during pregnancy in the Glasgow area. Following brief overviews of toxicology and the main problems facing the paediatric toxicologist, the development of analytical toxicology procedures to help to overcome them is summarised along with a more detailed examination of solid phase extraction (SPE) - theory, advantages and applications to biological samples. The initial experimental work established the feasibility of performing a full drug screen on small samples of blood such as those obtained from neonates, having a volume of 1-2ml. This used a single SPE cartridge for the extraction of a mixture of acidic and basic drugs followed by end-step analysis with enzyme immunoassay (ELA) and gas chromatography-mass spectrometry (GC/MS). Representative drugs from each group were selected for evaluation purposes: butobarbitone, amylobarbitone, methaqualone, primidone, and phenytoin drugs for the acidic drug group and cocaine, ecgonine methyl ester, morphine, diazepam, and desmethyldiazepam for the basic drug group. These were chosen as examples of drugs commonly used in the UK. Four analytes (morphine, methadone, cocaine and benzoylecgonine) were used to compare two different SPE cartridges, Bond Elut Certify® and Abselut®, which can be used to extract both acidic and basic drugs. The comparison involved four parameters: analyte recovery, lower limits of detection, presence of interferences in the extracts and analysis time required by each. Recoveries were in the range 60-100% and lower limits of detection were in the range 1-25 ng/ml and it was assessed that Bond Elut columns were better than Abselut columns.