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analytical method for chiral metabolites of methamphetamine and amphetamine

Methamphetamine/ Amphetamine Background. Primary drug threat in California1,872 clandestine lab seizures in 2001Most illegal labs are located in Northern California and MexicoClassified as a Schedule II drug by DEA. Methamphetamine Background. Enantiomers of Amphetamine and Methamphetamine. Cardiovascular activity.

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analytical method for chiral metabolites of methamphetamine and amphetamine

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    1: Analytical Method for Chiral Metabolites of Methamphetamine and Amphetamine CHINYERE WILLIAMS University of California, Davis UCLEADS, McNair Scholar 2002 UCSF Summer Research Training Program

    3: Primary drug threat in California 1,872 clandestine lab seizures in 2001 Most illegal labs are located in Northern California and Mexico Classified as a Schedule II drug by DEA Methamphetamine Background

    4: Enantiomers of Amphetamine and Methamphetamine

    5: Human Metabolism of Methamphetamine in vivo

    6: Why Analyze p-OH? According to Buttar, et. al, metabolic p-OH is twice as potent to the CNS and cardiovascular system as the parent d-, l-methamphetamines, and d-, l-amphetamines They have been linked to: Lowered birth weights Increased newborn mortality Head-twitching Enhancement of memory (not necessarily good memories)

    8: Hypothesis A method can be created to identify and quantify chiral parent drugs and their metabolites in biological samples such as urine using GC-MS

    9: Why Is This Study Necessary? Very little research on human subjects Fulfill a need for more accurate methods of analysis for metabolic enantiomers of drugs Gain a better understanding of the behavioral and physiological effects of methamphetamine abuse

    10: How The Study Is Conducted & Methodology

    11: What’s Being Analyzed?? Volunteers admitted to Langley Porter at Parnassus campus Set amount of methamphetamine given to subject Blood plasma and urine samples sent to labs for analysis

    13: Example of Final Derivatized Products

    14: MS Instrumentation Schematic

    15: Results

    16: (d)-p-OH-Methamphetamine Derivative

    17: (l)-p-OH-Methamphetamine Derivative

    18: (d)-p-OH-Amphetamine Derivative

    19: (l)-p-OH-Amphetamine Derivative

    20: Discussion & Conclusions

    21: Discussion Both p-OH-Methamphetamine and p-OH-Amphetamine exhibited extraction recoveries of approximately 80% Recovery of methamphetamine and amphetamine were approximately 100%

    22: Conclusions Following this methodology, chiral metabolites of methamphetamine and amphetamine can be resolved using GCMS analysis

    23: Acknowledgements

    24: References Buttar HS, Moffatt JH, Foster BC. Developmental toxicity of 4-substituted amphetamines in mice. Reprod Toxicol 1996 Jul-Aug;10(4):301-1. Holdefer RN, Jensen RA. The effects of peripheral D-amphetamine, 4-OH amphetamine, and epinephrine on maintained discharge in the locus coeruleus with reference to the modulation of learning and memory by these substances. Brain Res 1987 Aug 4;417(1):108-17. Shah V.P., Midha K.K., Findlay J.W.A, Yacobi A. Bioanalytical Method Validation - A Revisit with a Decade of Progress. Pharmaceutical Research, 2000 Dec; 17(12):1551-7. Tadano T, Satoh S, Kisara K. Head-twitches induced by p-hydroxyamphetamine in mice. J Pharmacol 1986 Aug;41(4):519-23.

    25: Analytical Method for Chiral Metabolites of Methamphetamine and Amphetamine CHINYERE WILLIAMS University of California, Davis UCLEADS, McNair Scholar 2002 UCSF Summer Research Training Program

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