Detection of Cocaine in Seized Drug Samples by Capillary Electrophoresis Tandem Mass Spectrometry
A methodology using capillary electrophoresis with tandem mass spectrometry detection (CE-MS/MS) was developed, and applied to determine the cocaine content of seized drugs. The cocaine separation among other concomitants by capillary electrophoresis was achieved in just 4.0 minutes using 30 mM ammonium formate, pH 6.5, as a background electrolyte (BGE). The correlation coefficient of the calibration curve in the range of 0.02 to 1 μg/mL was upper 0.999, and the limits of detection (LOD) and limits of quantification (LOQ) were 0.003 μg/mL and 0.01 μg/mL, respectively. The relative standard deviation repeatability (intraday and interday) was less than 6.5% (peak area). The analysis of seized suspected illegal drugs revealed the presence of cocaine in 93% of samples (n = 11), in amounts ranging from 0.04 to 429 mg/g, showing a high variability of concentrations of cocaine. The user can change the provider and, due to the large variability of concentration, be lead to an accidental overdose.
Segmental analysis for cocaine and metabolites by HPLC in hair of suspected drug overdose cases.
Hair samples of eight postmortem cases were analyzed in segments of 1 to 3 cm for cocaine, benzoylecgonine and cocaethylene. Samples were prepared for analysis by digestion in 0.1 M HCl and subsequent extraction with mixed-mode solid-phase extraction columns. Measurement was made by reversed-phase, narrow-bore HPLC and fluorescence detection using two laboratory-made internal standards. The concentrations were in the region of 0.29-316 ng/mg of hair for cocaine, 0.43-141 ng/mg of hair for benzoylecgonine and 0.93-1.83 ng/mg of hair for cocaethylene. All eight investigated cases had cocaine-positive segments. In six of the cases, all segments were positive, suggesting regular cocaine use and two showed in-between negative segments indicating an interruption or a change of the abuse intensity. The results showed a second, remarkable observation, i.e. enormous concentration differences (factor >150) for both cocaine and benzoylecgonine between the different subjects. Furthermore, interindividual cocaine/benzoylecgonine ratios ranged from 0.02 to 8.43. We believe these observations could in part be attributed to both some of the still existing limitations in the analytical approach(es), especially the mandatory hair washing steps, and in our still too limited knowledge of the hair incorporation processes. Nevertheless, in some cases, segmental analysis proved to be an important tool to distinguish, together with postmortem examination, deadly chronic abuse from single acute drug overdosage.
Pharmacokinetics of Mivacurium Isomers and Their Metabolites in Healthy Volunteers after Intravenous Bolus Administration
Background Previous studies report the pharmacokinetics of mivacurium isomers after an infusion using venous blood sampling. Although the extent of the mivacurium arterial‐venous gradient is not known, the sampling site is likely to influence mivacurium pharmacokinetic parameters because the drug is rapidly metabolized as it traverses the circulation. The objectives of this study were (1) to determine the pharmacokinetics of mivacurium isomers in healthy persons after intravenous bolus administration using intensive arterial blood sampling, and (2) to characterize the formation and elimination of mivacurium metabolites in human plasma. Methods Eight persons classified as American Society of Anesthesiologists physical status 1 or 2 who were scheduled to undergo elective surgery under balanced anesthesia received 0.15 mg/kg mivacurium chloride as an intravenous bolus. Arterial blood samples were collected every 10 s during the first 2 min and at frequent intervals for 4 h thereafter. Plasma concentrations of mivacurium isomers and their metabolites were determined by two stereoselective high‐performance liquid chromatographic methods coupled with fluorometric detection and noncompartmental pharmacokinetic parameters. Results Mean elimination half‐lives of the trans‐trans, cis‐trans, and cis‐cis isomers were 2.4, 2, and 28.5 min, respectively, with corresponding mean plasma clearances of 29.2, 45.7, and 6.7 ml [center dot] min‐1 [center dot] kg‐1. The volumes of distribution at steady state of the trans‐trans, cis‐trans, and cis‐cis isomers were 0.047, 0.054, and 0.189 l/kg, respectively. Plasma concentrations of monoester and alcohol metabolites peaked 25 s (median) after mivacurium injection, with half‐lives in the range of 90 min, except for the cis alcohol metabolite, which was only negligibly and transiently formed. Conclusions Substantial hydrolysis of mivacurium isomers by cholinesterases was confirmed by the rapid appearance of mivacurium metabolites in plasma. The intensive arterial sampling proved to be critical for the trans‐trans and cis‐trans isomers because the area under the curve between 0 and 2 min accounted for 75% and 86% of the total, respectively.