Egleton, Thomas Abbruscato, in Advances in Pharmacology, 2014 5.2 AmphetaminesĬhanges in catecholamine signaling are the hallmark of amphetamines. Methods for analysis of AMP and related compounds in meconium are summarized in Table 29.2. Additionally, fetal CYP2D6 activity is known to be present but its activity toward MAMP and its related metabolites is unknown. The authors acknowledge that CYP2D6 has greater than 70 known allelic variants and its activity is increased in pregnancy. The biotransformation of MAMP to AMP and pOHMAMP by CYP2D6 may play a role in variability of detection. Despite increases in detection of MAMP exposure, the addition of pOHMAMP did not increase the confirmation rate of positive immunoassay results. Detection of pOHMAMP was also associated with lower birth weight and younger maternal age although not in a linear fashion. The detection of pOHMAMP was loosely correlated with continued MAMP use in the third trimester and occurred at higher concentrations. For six samples it was the only AMP metabolite present in the meconium specimen. Addition of pOHMAMP increased positive detection by 14%. The third group was positive self-reported MAMP use with positive immunoassay results. The second was positive self-reported MAMP use with negative immunoassay results. The first set was negative self-reported MAMP use with positive immunoassay results. Meconium collected from the infants of three sets of women was evaluated. This group later expanded upon their earlier work by applying the method for additional AMP metabolites to 132 meconium samples irrespective of initial immunoassay screening results for AMPs. There was no correlation of MAMP concentration with HMMA or norephedrine. There was a correlation between MAMP concentrations with AMP and pOHMAMP. Norephedrine and HMMA were present in 25% and 18% of samples, respectively. Analysis revealed that after MAMP and AMP, pOHMAMP was the most abundant metabolite present with 86% of samples being positive for this compound. One year later, work from the same group was published that applied this method to 43 meconium specimens to investigate the deposition of various metabolites including para-hydroxyamphetmaine (pOHAMP), para-hydroxy methamphetamine (pOHMAMP), HMA, 4-hydroxy-3-methoxymethamphetamin (HMMA), norephedrine in meconium. The elevated limit of quantitation for 4-hydroxy-3-methoxyamphetamine (HMA) was attributed to background interference present in blank meconium with the HMA qualifier transition ion. The lower limit of quantitation (LOQ) ranged from 1.25 to 40 ng/g. Liquid chromatographic separation occurred over 15 min followed by an 18 min equilibration. Using liquid–liquid extraction for 30 min followed by SPE cleanup, the calculated extraction efficiencies ranged from 68.8% to 86.8%. The second curve ranged from 125 to 10,000 ng/g and used a 1 µL injection. The first curve ranged from 1.25 to 2500 ng/g and used a 10 µL injection. To accommodate this, two calibration curves utilizing two different injection volumes were validated. This makes creating a single calibration curve spanning several factors of 10 challenging. Minor metabolites may only be present at much lower concentrations. AMP and MAMP have been reported to be present at concentrations exceeding 1000 ng/g in meconium samples. The challenge for analysis of both parent and metabolite compounds is due to the extreme variation in concentration. from the National Institutes of Health (NIH) have developed and validated an LC/Ms/MS method for analysis of 10 AMPs and metabolites in meconium. There is currently limited data investigating the effects of in utero exposure to AMP, methamphetamine (MAMP), and 3,4-methylenedioxymethamphetamine (MDMA) alone or in conjunction with other drugs. Cotten, in Critical Issues in Alcohol and Drugs of Abuse Testing (Second Edition), 2019 Analysis of AmphetamineĪlthough amphetamine (AMP) abuse is currently not as prevalent when compared to opiate abuse in the United States, emerging data from 2018 suggests AMP abuse is increasing.
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