John T. Cody

Determination of methamphetamine enantiomer ratios in urine by gas chromatography-mass spectrometry

Analysis of the enantiomers of methamphetamine and its metabolite amphetamine is an extremely important process for a number of scientific disciplines. From studies of biological activity and mechanisms through determination of precursor molecules in a criminal investigation are all served by this analytical procedure. Utilization of gas chromatography-mass spectrometry with chiral derivatizing reagents is the most common chiral procedure and produces excellent results. Of the chiral derivatizing reagents available, the most widely used is trifluoroacetyl-l-prolyl chloride (TPC). Utilization of other derivatives require either synthesis by the analyst or have not shown themselves to provide as good a separation as did the TPC reagent. Use of chiral stationary phases yield good results but the disadvantages of temperature limits of these columns and the narrow use to which the columns can be put has limited their utilization. A significant utility of the chiral stationary phase is the ability to determine the purity of a chiral derivatizing reagent. Even if not used for routine analysis of enantiomers, utilization of this procedure can determine the purity of a reagent such as TPC and allow for accurate calculation of actual amounts of each enantiomer. This can be estimated using chiral derivatives on an achiral column, but it is limited to the extent that it is not able to differentiate enantiomeric impurity in the reagent versus the drug itself. Description of chromatographic procedures primarily focusing on gas chromatographic-mass spectrometric techniques but also including liquid chromatographic techniques along with examples of extraction and derivatization procedures is the focus of this review.

Enantiomeric composition of amphetamine and methamphetamine derived from the precursor compound famprofazone

Fourteen different metabolic precursors of amphetamine or methamphetamine have previously been identified. Many of these drugs are available only by prescription and several are only available in some parts of the world and not in others. One of these drugs, famprofazone, is available over-the-counter which complicates the interpretation of methamphetamine urine drug testing results. To assist in the interpretation of typical laboratory results, a study was conducted to determine the enantiomeric composition of the methamphetamine and amphetamine produced from the metabolism of famprofazone. Fifty mg of famprofazone was administered to a volunteer followed by collection of urine for the next 6 days. The resulting quantity, enantiomeric composition and percent conversion from famprofazone to the product amphetamine and methamphetamine was determined. The results showed the amphetamine and methamphetamine to include both the d- and l-enantiomers. Percent conversion and peak concentrations were similar to those reported in previous studies.

Metabolic Production of Amphetamine Following Administration of Clobenzorex

Many of the anorectic drugs that are metabolized to amphetamine and/or methamphetamine pose significant concerns in the interpretation of amphetamine-positive drug testing results. One of these drugs--clobenzorex--has been shown to produce amphetamine. Thirty milligrams of clobenzorex hydrochloride, in the form of a single Asenlix capsule (Roussel, Mexico), were administered orally to five human volunteers with no history of amphetamine, methamphetamine or clobenzorex use. Following administration, urine samples (total void volume) were collected ad lib for seven days and pH, specific gravity and creatinine values were determined. To determine the excretion profile of amphetamine and parent drug, samples were extracted, derivatized, and analyzed by gas chromatography/mass spectrometry (GC/MS) using a standard amphetamine procedure with additional monitoring of ions at m/z 91, 118, 125 and 364 for the detection of clobenzorex. Peak concentrations of amphetamine were detected at 4 to 19 h postdose and ranged from approximately 715 to 2474 ng/mL amphetamine. Amphetamine could be detected (> 5 ng/mL) in the urine in one subject for up to 116 h postdose. GC/MS was also used to determine the enantiomeric composition of the metabolite, amphetamine. This analysis revealed the metabolically derived amphetamine was only the d-enantiomer. This differs from previous literature which indicates clobenzorex is the racemic N-orthochlorobenzyl derivative of amphetamine.

The pharmacokinetics of oxytocin as they apply to labor induction.

OBJECTIVE Our purpose was to determine the relationship among plasma oxytocin levels, metabolic clearance rate of oxytocin, and uterine activity in gravid women undergoing labor induction. STUDY DESIGN Ten women receiving oxytocin for labor induction and agreeing to participate had blood sampled before initiation of oxytocin and at different levels of uterine pressure. Samples were analyzed with 200 microliter extracts from 1 ml of plasma with an oxytocin radioimmunoassay. The intraassay coefficient of variation was < 3%. Sensitivity of the assay was 1.5 pg/ml. Pharmacokinetic parameters including plasma levels and metabolic clearance rates were calculated. Data were analyzed with the paired t test and linear and logistic regression. RESULTS Mean oxytocin levels and metabolic clearance rates were 26.6 pg/ml and 7.97 ml/min. There was no correlation between changes in oxytocin level and metabolic clearance rate. Increases in infusion rates were correlated with increases in oxytocin levels (r = 0.71, p < 0.001). Cervical dilatation and uterine contraction pressures did not correlate with oxytocin levels. CONCLUSION Peripheral plasma levels of oxytocin may not accurately reflect uterine activity or progress in labor. Plasma levels of oxytocin may merely reflect the rate of oxytocin infusion.