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We determined the urinary excretion of MAMP after oral ingestion and examined the effect of using lower cutoffs on detection of exposure. After ingestion, the volunteers collected all urine specimens for 2 weeks. After solid-phase extraction, MAMP and AMP were measured by gas chromatography—positive chemical ionization mass spectrometry with dual silyl derivatization. Conclusions: At the lower cutoff, initial detection times are earlier, detection windows are longer, and confirmation rates are increased. Elimination of the AMP requirement would increase detection rates and allow earlier detection.
Worldwide, trafficking of amphetamine-type stimulants increased more than any other drug class during the s, and seizures quadrupled 3. Abuse of the stimulant MAMP is attributable to its potent dopaminergic and sympathomimetic effects, including euphoria, improved cognitive and sensory performance, generalized improvement in mood, increased physical endurance, and appetite suppression 4 5 6 7 8.
Negative sequelae are generally attributable to exaggerated central nervous system and cardiovascular effects 4 6 8 9 11 15 16 17 18 19 and include psychosis, paranoia, hyperpyrexia, seizures, stroke, tachycardia, arrhythmias, pericarditis, myocardial ischemia, hypertension, aortic and cerebral aneurysm dissection, and myocardial infarction. MAMP is excreted primarily in urine, with little biliary excretion of the parent drug or How long are amphetamines detectable in urine Each unit increase or decrease in urinary pH produces a respective 7-h increase or decrease in the MAMP plasma half-life It has also been reported that the renal clearance of MAMP exceeds that of the average renal filtration rate, suggesting the involvement of an active transport mechanism in the excretion of MAMP AMP requirements were instituted because of the potential for false-positive analytical with specimens containing other sympathomimetic amines The object of this study was to characterize the urinary excretion of MAMP and its major active metabolite, AMP, in humans after controlled oral administration.
Urine concentration data were evaluated to determine detection windows and confirmation rates based on current and proposed confirmation cutoffs and cutoffs based on MAMP requirements alone.
Methanol, methylene chloride, 2-propanol, and acetonitrile were HPLC-grade chemicals. All other chemicals were reagent grade. Qualitative and quantitative analyses were performed on a Hewlett-Packard gas chromatograph interfaced with a Hewlett-Packard mass selective detector. The single quadrupole mass spectrometer was operated in positive chemical ionization PCI mode with methane as reactant gas as described ly Participants were healthy volunteers with a history of stimulant and opioid use.
Participants were evaluated medically and psychologically before admission to the clinical ward to establish their health. Their vital s were monitored daily, and routine blood testing CHEM Profile 2 was performed on alternate weeks for medical evaluation throughout the study. Participants were not physically dependent on illicit drugs. During the study, periodic urine specimens were tested to ensure that there was no self-administration of drugs. The first 2 weeks of the study served as a clearance phase for ly self-administered drugs. Morning urine specimens were collected during this time.
Drug How long are amphetamines detectable in urine occurred in weeks 3 and 7. As part of the pharmacodynamic study, participants were administered placebo MAMP capsules in week 6. Participants were scheduled to receive four consecutive daily administrations of the sustained-release formulation, the only form of MAMP available for therapeutic administration at the time of this study. Abbott Laboratories discontinued production of Desoxyn Gradumet in ; the Desoxyn formulation is currently available.
If physiologic measures i. However, participants always received four doses once daily within 7 days. We therefore have grouped the data into three : single, consecutive, and nonconsecutive administration regimens see section on data analysis. The total base equivalent amounts of MAMP administered in the low- and high-dose regimens were Three participants did not receive the high-dose regimen because of personal choice, medical disqualification, or behavioral misconduct.
All drug administrations were conducted under subject-blind conditions. Urine specimens were collected ad libitum after initiation of the dosing regimen. Specimens were collected in polypropylene bottles, and void volumes were recorded. Calibrators and controls were prepared in urine that was collected from laboratory volunteers and was demonstrated to be negative for MAMP and AMP by GC-MS analysis before use in the preparation of calibrators and controls.
Two dynamic linear ranges were established for the assay.
Quantitative analysis was performed by use of split curves at concentration ranges of 2. Specimen samples were analyzed using the curve with the appropriate dynamic range. Calibrators and controls were prepared from different commercially available drug lots and by different analysts.
Linear regression analysis of control samples containing 10 and ng of drug were performed using the 2. Calibrators, controls, and specimens were processed by SPE according to a ly published method Briefly, 1 mL of urine was aliquoted, ng of each internal standard was added, and samples were adjusted to acidic pH with 0. Analytes were isolated on preconditioned SPE columns and eluted with methylene chloride—2-propanol—ammonium hydroxide by volume. This dual derivatization scheme was originally developed as a method for the analysis of multiple basic drug classes.
Confirming ions, retention order, and derivatives are listed in Table 1. Urine specimen analyte concentrations were determined in selected ion monitoring mode. The initial detection time after first administration and final detection time after last administration were defined as the first and last specimens positive at or above respective cutoffs.
The percentage detection rate was determined by dividing the of positive specimens collected over a time period by the total of specimens collected over the same time period and multiplying by Mean detection rates were determined by averaging rates from all participants over a collection period. Total detection rates were also determined by dividing the sum of all positive specimens from all participants by the total of specimens collected over a collection period. Individual, mean, and total h detection rates were determined after single doses.
Ranges and means for final detection times and voidtotal urine specimens collected from first drug administration to last positive specimen, How long are amphetamines detectable in urine positive specimens from initial dosing to last positive specimen, and total detection rates across participants and doses were also determined.
The percentage of MAMP eliminated in urine after each administration regimen was determined by dividing the total amount of MAMP excreted by the total amount of base drug administered in the low- and high-dose regimens All single-administration data were collected after low-dose administrations. Administrations were considered single if specimens from five consecutive urine voids collected immediately before the next dosing were negative for both MAMP and AMP at their respective LOQ.
Nonconsecutive administrations had random 2- to 4-day intervals between administrations. With the 2. After the first drug administration of each regimen, measurable concentrations of both MAMP and AMP initially How long are amphetamines detectable in urine in the first to fourth void collected, and no dose-detection time or regimen-detection time relationship was observed Tables 2 and 3. Consecutive, four consecutive daily administrations; Nonconsecutive, four nonconsecutive daily administrations within 7 days; Single, single administration preceded by five or more specimens negative for MAMP and AMP at their respective LOQ.
Peak AMP concentrations after single-administration regimens occurred in the 2nd to 29th void collected at The total amount of AMP How long are amphetamines detectable in urine ranged from 1. Large intersubject variability in AMP-MAMP ratios were observed, whereas intrasubject ratios after consecutive administration consistently increased over time.
This volunteer was the only participant to receive consecutive administrations of the low and high doses, but these patterns were consistent across participants. A correlation between regimen and detection rate was not observed. Final detection times and total detection rates across MAMP doses and administration regimens. Initial detection voids and times after the first low and high MAMP administration are listed in Tables 2 and 3.
There were no ificant differences observed in final detection times from last drug administration across regimens or doses Tables 6 and 7. The time to last positive from the last drug administration was 22—66 Detection rate also appeared to be correlated with micturition interval.
Generally, detection rate increased with longer micturition intervals. Tables 6 mg dose and 7 mg dose list the final detection times from the last dose by regimen. Across doses, final detection times were 25—77 Final detection time from last drug administration was 25—77 mean, In three instances, final detection time also increased by 6—10 h. MAMP is abused for its euphoric and performance effects. Reports indicate that truck drivers, construction workers, young professionals, and students commonly self-administer single doses of MAMP to improve performance and to prevent or reverse somnolence However, even low single doses 0.
Identification of both habitual and occasional abusers is an important component of medical, workplace, criminal justice, military, and forensic drug testing programs. Therefore, it is important to describe the urinary excretion of MAMP and AMP after controlled administration of single and multiple doses of MAMP and to evaluate the effects of cutoff changes on detection times and rates after these regimens.
from these studies should help determine interindividual differences in metabolism and excretion of MAMP.How long are amphetamines detectable in urine
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Amphetamine Detection Window