Optimization of Pretreatment Parameters in Hair Analysis for Drugs of Abuse and Understanding Protein-Drug Physicochemical Interactions

Because of a lack of understanding of the modes of interaction between drugs of abuse and human hair, hair is not routinely used in toxicological analysis. Using hair samples, rather than urine or blood samples, to detect and identify drugs offers two major advantages. First, it provides a longer window of time for detection. Second, hair samples are particularly well suited to establishing the timeline of drug use because the growth rate of hair is well established. The applicant proposes to address this challenge through research to optimize pretreatment methodologies and determine the relative proportions of selected drugs of abuse held in hair.

"Note: This project contains a research and/or development component, as defined in applicable law," and complies with Part 200 Uniform Requirements - 2 CFR 200.210(a)(14).

nca/ncf

Previous literature suggests that there are different modes of interaction between drugs of abuse and human head hair. The ambiguity of these interactions has resulted in criticism of the routine use of hair as a biological matrix for toxicological analysis. The aims of the present research are to address these issues by comparing the most common pre-analytical methods to prepare hair samples and to investigate the interactions that drugs have with the hair matrix, namely keratin and melanin. Pretreatment steps in the analysis of drugs in human hair include decontamination, segmentation, extraction, and purification. Optimizing extraction is essential to accurately identify and quantify drugs present in a hair sample. Different mechanisms to free drugs from the hair are typically utilized; base or enzymatic degradation or solvent extraction. A comparative analysis of the recovery of drug resulting from different extraction methods, which has not yet been reported, will provide insight into the types of interactions that occur between drugs and hair. Determining effective extraction methods requires an understanding of how the compounds of interest are held in the matrix. A consensus from the Society of Hair Testing has emerged regarding the routes of exposure of head hair to drugs of abuse, but the nature of the physicochemical interactions between the biological matrix and these substances has not been fully explored. Thus, the second aim of this research is to determine if they are covalent, non-covalent, or a combination thereof. Investigating the use of hair as a biological matrix is important because this matrix is particularly well suited for establishing the time-line of drug administration beyond just a few hours or days, as is the case with blood and urine specimens. The greater window of detection for drugs of abuse in hair allows for the detection of compounds of interest when urine and blood testing fail. Establishing a database exploring the interactions of hair and drugs and identifying the best methodology for related analyses is paramount for the routine use of hair as an acceptable biological matrix for forensic toxicological analysis. This research proposes to contribute to this database by optimizing existing pretreatment methodology and by determining the relative proportions of selected drugs of abuse that are held in hair due to covalent vs. non-covalent interactions. Research findings from this project will be disseminated in a doctoral dissertation, published peer-reviewed articles, NIJ reports, and in presentations at national scientific meetings.

"Note: This project contains a research and/or development component, as defined in applicable law," and complies with Part 200 Uniform Requirements - 2 CFR 200.210(a)(14). NCA/NCF

Previous literature suggests that there are different modes of interaction between drugs of abuse and human head hair. The ambiguity of these interactions has resulted in criticism of the routine use of hair as a biological matrix for toxicological analysis. The aims of this research are to address these issues by comparing the most common pre-analytical methods to prepare hair samples and to investigate the interactions that drugs have with the hair matrix, namely keratin and melanin. Pretreatment steps in the analysis of drugs in human hair include decontamination, segmentation, extraction, and purification. Optimizing extraction is essential to accurately identify and quantify drugs present in a hair sample. Different mechanisms to free drugs from the hair are typically utilized; base or enzymatic degradation or solvent extraction. A comparative analysis of the recovery of drug resulting from different extraction methods, which has not yet been reported, will provide insight into the types of interactions that occur between drugs and hair. Determining effective extraction methods requires an understanding of how the compounds of interest are held in the matrix. A consensus from the Society of Hair Testing has emerged regarding the routes of exposure of head hair to drugs of abuse, but the nature of the physicochemical interactions between the biological matrix and these substances has not been fully explored. Thus, the second aim of this research is to determine if they are covalent, non-covalent, or a combination thereof. Investigating the use of hair as a biological matrix is important because this matrix is particularly well suited for establishing the time-line of drug administration beyond just a few hours or days, as is the case with blood and urine specimens. The greater window of detection for drugs of abuse in hair allows for the detection of compounds of interest when urine and blood testing fail. Establishing a database exploring the interactions of hair and drugs and identifying the best methodology for related analyses is paramount for the routine use of hair as an acceptable biological matrix for forensic toxicological analysis. This research proposes to contribute to this database by optimizing existing pretreatment methodology and by determining the relative proportions of selected drugs of abuse that are held in hair due to covalent vs. non-covalent interactions. Research findings from this project will be disseminated in a doctoral dissertation, published peer-reviewed articles, NIJ reports, and in presentations at national scientific meetings. ca/ncf