Xiang, Ping (2011) Hair analysis for drugs of abuse. Doctoral thesis, University of central Lancashire.
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This thesis covers a range of important issues in hair analysis and includes 27 scientific works in which the name of the candidate was either listed as the first author or as the major contributor. The work presented in this thesis involved the development of a series of analytical methods to detect trace amounts of drugs in hair and also investigated the mechanisms by which drugs may be incorporated into hair. The major areas covered in this study can be summarized as follows:
1. The methods for the identification and quantification of opiates, amphetamines, ketamine, cannabis, cocaine, benzodiazepines, antidepressants, antipsychotics, and anabolic steroids in hair were developed using gas chromatography–mass spectrometry (GC-MS), liquid chromatography–tandem mass spectrometry (LC-MS/MS) and gas chromatography–tandem mass spectrometry (GC-MS/MS). With GC-MS methods, the limits of detection were 0.1-0.5 ng mg-1 of hair for antidepressants and antipsychotics. For illegal drugs, hair specimens were analyzed by GC-MS with limits of detection of 0.02-2ng mg-1. GC/MS/MS is more sensitive than GC-MS to detect these drugs in hair. The lower limits of detection ranged from 0.001 to 0.020 ng mg-1 for 21 anabolic androgenic steroids and their esters in hair using liquid chromatographic-tandem mass spectrometric method. And the limits of detection ranged from 0.2 to 5 pg mg-1 for benzodiazepines in hair. Tandem mass spectrometry is characterized by its sensitivity, selectivity and specificity, which makes it particularly suitable for the analysis of trace amount of target analytes in hair.
2. Usually, screening for drugs of abuse is the first step in clinical and forensic toxicology. There are a large number of controlled substances and doping agents and novel compounds, which have yet to be characterised. A series of screening methods for drugs of abuse in hair were developed using LC-MS/MS and GC-MS/MS. Using our own library of MRM transitions, the optimum collision energies selected for each transition and retention times were set up. These methods have been applied successfully in forensic casework.
3. Of growing importance to the field of hair analysis is the detection of metabolites related to the parent drugs. Demonstrating the presence of a metabolite of a drug (such as, heroin, amphetamines, cocaine, meperidine, ketamine, triazolam or psychotropic drugs) provides compelling evidence for exposure to the parent drug, and permits distinction between external contamination from ingestion and facilitation of the interpretation of results. The presence of antidepressant and antipsychotic drugs and their metabolites in the hair of psychiatric patients was investigated using GC-MS-EI and GC-MS-PCI. The parent drug and its major metabolite, such as opiates (morphine, 6-acetylmorphine), methamphetamine (methamphetamine, amphetamine), ketamine (ketamine, norketamine), cocaine (cocaine, benzoecognine), meperidine (meperidine, normeperidine), triazolam (triazolam, α-hydroxytriazolam), and clonazepam (clonazepam, 7-aminoclonazepam) were quantified in authentic hair samples simultaneously. The differences were finding in the ratio of parent drug to metabolite. For illegal drugs, the concentrations of parent drugs were higher than that of their metabolites. The results of triazolam and clonazepam were contrary. These data are suitable reference values and are the basis for the interpretation of results.
4. The mechanisms by which drugs are incorporated into hair are not fully understood. Based on experiments with guinea pigs with black, white, or brown hair, the mechanisms of incorporation of cocaine, methamphetamine, ketamine, triazolam and anabolic steroids into hair were investigated. The concentrations of drugs in hair were found to be related to physicochemical properties of drugs. The parent drugs were the predominant analytes in hair. There was an obvious relationship between the concentration of drugs in hair and hair pigmentation. The concentrations of drugs deposited in black hair was found to be higher than that in brown and white hair samples, even when comparing results using hairs on the same multicoloured animal body. This work confirmed that melanin affinity is a governing factor in drug incorporation into hair shafts. These studies on the distribution of drugs in the hair shaft and how their concentration changes along the shaft provide information relevant to the time of ingestion and substance use/abuse.
5. In recent years an increase in drug-facilitated sexual assault (DFSA) has been reported. Segmental hair analysis has proved useful in widening the window of detection, as blood and urine analyses are of limited use, due to the long delays between the actual assaults and obtaining samples from suspects that are frequently encountered in investigations of such crimes. In China, benzodiazepines are the most frequently observed compounds in cases of drug-facilitated crime. In a paper reported here, 14 volunteers ingested a single 1-6 mg estazolam tablet to permit the evaluation of segmental hair analysis after a single drug dosage. Hair was collected one month after administration of the drug. All the proximal segments tested positive for estazolam. With increased dosage, estazolam could be detected in the 2-4 cm segments nearest the hair root in some subject’s hair shafts. In some cases, the 4-6 cm segments also tested positive. Hair analysis was applied to samples from two authentic criminal cases. A significant variation was observed between those obtained from previous studies and the results presented here. The intersubject variability in segmental analysis can be explained mainly due to melanin content and diffusion from sweat or other secretions during formation of the hair shaft. However, more substantial procedural and interpretation guidelines are required to use segmental hair analysis in drug-facilitated crimes. On the other hand, the minimal dosage for detection, which is a critical but previously unknown threshold value of fundamental importance in hair analysis, was determined for triazolam and ketamine in guinea pig hair.
6. Doping with endogenous anabolic steroids is one of the most serious drug issues in sports today. The measurement of anabolic steroid levels in human hair permits the distinction between pharmaceutically produced steroids and naturally occurring steroids. Full-length hair samples were taken at the skin surface from the vertex of 39 males, 30 females and 11 children from China. None of the subjects were professional athletes. Testosterone and dehydroepiandrosterone were detected in all the hair segments. The physiological concentrations of testosterone were in the range 0.8-24.2 pg mg-1, 0.1-16.8 pg mg-1 and 0.2-11.5 pg mg-1 in males, females and children, respectively. However, the mean values of dehydroepiandrosterone were much higher than those for testosterone. This is the first investigation into the physiological concentrations of anabolic steroids in human hair in Chinese subjects. These data provide suitable reference values and form the basis for the interpretation of results from investigations into the abuse of endogenous anabolic steroids.
In conclusion, the work presented in this study demonstrates that there was a good correlation between the concentration of drugs in hair and drug dosage. There was an obvious relationship between hair drug concentration and hair colour. Melanin affinity is shown to be a governing factor in determining drug incorporation into hair, and the concentration of drugs deposited in black hair was found to be higher than that in brown and white hair samples. This thesis provides data that will be useful in the application of hair analysis regarding drugs of abuse and in the interpretation of toxicological results.
|Item Type:||Thesis (Doctoral)|
|Additional Information:||The work presented in this thesis involved the development of a series of analytical methods to detect trace amounts of drugs in hair and also investigated the mechanisms by which drugs may be incorporated into hair. 1. These methods maybe have some similarities with others, but the target analytes were partly different. Our methods are more focuses on the simultaneous determination of parent drugs and their metabolites. The methods we established were improved to extend the screening range of detecting drugs of abuse in hair and promote the applications of MS/MS. 2. For the first time, studies on ketamine, meperidine, antipsychotic and antidepressant drugs in hair. In our experiment, the presence of hair with different colours in the same guinea pig hair samples effectively minimized variability due to individual differences and other inter- and intra-factors such as living condition, age and health condition. The mechanisms by which drugs are incorporated into hair are not fully understood. These studies provide useful information for the interpretation of hair analysis results. 3. For the first time, the time courses of deposit of eight anabolic steroids in guinea pig hair were determined. Physiological concentrations of anabolic steroids in human hair in Chinese subjects were determined. These data are suitable reference values and are the basis for the interpretation of results.|
|Uncontrolled Keywords (separate with ;):||Hair analysis; drugs of abuse; liquid chromatography–tandem mass spectrometry; incorporation; a single dose|
|Subjects:||Q Science > Q Science (General)|
Q Science > QD Chemistry
R Medicine > RM Therapeutics. Pharmacology
|Schools:||College of Science and Technology > School of Forensic and Applied Sciences|
|Deposited By:||Helen Cooper|
|Deposited On:||05 Jan 2012 12:02|
|Last Modified:||11 Feb 2014 14:26|
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