Improved methods to monitor treatment compliance and efficacy is an important goal of drug-abuse treatment programs and clinical trials for new treatment regimens. Monitoring drug use during pregnancy is also an important clinical goal. Compared to urine, plasma and blood, hair may provide a longer window to monitor for drugs and other compounds due to its slow growth and possible permanent retention of drugs. The presence of certain drugs and their metabolites has been demonstrated in human hair at times when plasma and urine drug concentrations are not measurable. The goal of this project is to acquire knowledge regarding the suitability of quantitative, segmental human hair analysis for determination of drug exposure in clinical settings. Specific marker substances will be used to establish reference points (with respect to time) in human hair. To achieve these objectives, the following specific aims are proposed: (1) To develop quantitative analytical methods for hair utilizing LC/MS/MS. Ultra-sensitive and specific procedures using liquid chromatography and tandem mass spectrometry will be developed for the combined detection and quantitation of a treatment drug (buprenorphine, 1-alpha-acetylmethadol, or methadone), drugs of abuse (morphine, heroin) and marker substances (phenazopyridine or ofloxacin) in hair. Also, specific and selective decontamination procedures will be developed to minimize the potential bias of environmental contamination of hair for drugs of interest and to maximize the reliability of measured quantitative drug concentrations. (2) To determine if quantitative analysis of hair can be used to evaluate recidivism and treatment compliance. Administration of a marker substance such as phenazopyridine or ofloxacin will be used to establish reference points in human hair between which drug use and treatment compliance or recidivism in clinical drug-abuse studies can be measured. We will also determine if quantitative measures of drug concentrations in hair are dependent upon the dose and route of drug administration. (3) To determine if quantitative analysis of hair can be used to evaluate fetal drug exposure in pregnant women receiving drug treatment. Specifically, we will determine if there is a relationship between maternal exposure to a treatment drug (methadone) during pregnancy and neonatal hair concentrations of methadone at birth. Preliminary data presented demonstrate that we are able to perform all aspects of this proposal and that we will clearly be able to progress from analytical methods development, to decontamination studies, to in vivo human and animal studies of marker substance incorporation into hair, and to studies of fetal drug exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA009096-05
Application #
2695823
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Singh, Hari
Project Start
1994-09-30
Project End
2002-08-31
Budget Start
1998-09-01
Budget End
1999-08-31
Support Year
5
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Utah
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
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Wilkins, Diana G; Mizuno, Atsuhiro; Borges, Chad R et al. (2003) Ofloxacin as a reference marker in hair of various colors. J Anal Toxicol 27:149-55
Kaufman, Jay S; Dole, Nancy; Savitz, David A et al. (2003) Modeling community-level effects on preterm birth. Ann Epidemiol 13:377-84
Rollins, Douglas E; Wilkins, Diana G; Krueger, Gerald G et al. (2003) The effect of hair color on the incorporation of codeine into human hair. J Anal Toxicol 27:545-51
Charles, Bradley K; Day, Jayme E; Rollins, Douglas E et al. (2003) Opiate recidivism in a drug-treatment program: comparison of hair and urine data. J Anal Toxicol 27:412-28
Savitz, David A; Henderson, Laura; Dole, Nancy et al. (2002) Indicators of cocaine exposure and preterm birth. Obstet Gynecol 99:458-65
Balu, Rukmini B; Savitz, David A; Ananth, Cande V et al. (2002) Bacterial vaginosis and vaginal fluid defensins during pregnancy. Am J Obstet Gynecol 187:1267-71
Savitz, David A; Terry Jr, James W; Dole, Nancy et al. (2002) Comparison of pregnancy dating by last menstrual period, ultrasound scanning, and their combination. Am J Obstet Gynecol 187:1660-6

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