Detection of cocaine and its metabolites in whole blood and plasma following a single dose, controlled administration of intranasal cocaine

Abstract

The disposition of drugs and their metabolites have been extensively described in the literature, based primarily on the analysis of plasma and urine. However, there are more limited data on their disposition in whole blood, which is often the only specimen available in forensic investigations and cases of driving under the influence of drugs. In this study, we have, for the first time, established pharmacokinetic properties of cocaine (COC) and its metabolites from concurrently collected whole blood and plasma samples, following a single 100 mg dose of cocaine hydrochloride administered via nasal insufflation to seven healthy volunteers. The median Cmax of COC and its major metabolites, benzoylecgonine (BZE) and ecgonine methyl ester (EME), were closely related in whole blood and plasma. The median Cmax for COC in plasma was 379.7 ng/mL (347.5–517.7) and 344.24 ng/mL (271.6–583.2) in whole blood. The median Cmax for BZE in plasma was 441.2 ng/mL (393.6–475. and 371.18 ng/mL (371.1–477.3) in whole blood, EME was 105.5 ng/mL (93.6–151.8) in plasma and 135.5 ng/mL (87.8–183) in whole blood. Calculated medians of the whole blood to plasma ratio of COC (0.76), BZE (0.98) and EME (1.02) of approximately 1, strongly suggesting that the erythrocyte cell wall presents no barrier to COC and its metabolites. Furthermore, whole blood and plasma concentrations of COC were strongly correlated (R2 = 0.0914 R = 0.956, p < 0.0001), as was BZE (R2 = 0.0932 R = 0.965, p < 0.0001) and EME (R2 = 0.0964R = 0.928, p < 0.0001). The minor oxidative metabolite norcocaine (NCOC) was detected in both whole blood and plasma at concentrations between 1 and 5 ng/mL within 60–180 minutes, suggesting that NCOC could be indicator of recent COC administration. Data from this study have shown for the first time that COC and its metabolites BZE and EME are evenly distributed between plasma and whole blood following controlled single‐dose intranasal COC administration.

Efficient Cocaine Degradation by Cocaine Esterase-Loaded Red Blood Cells

“…Indeed, since plasma cocaine concentration in a dependent subject could reasonably be in the 10-1000 ng/ml range (Schulz and Schmoldt, 2003), corresponding to 0.165-16.5 µmol/5 L blood, the infusion of 160 IU of E196-301 (see Table 2) will be extremely efficient in a rapid and complete cocaine degradation. This conclusion is also supported by two recent studies in which cocaine has been administered intravenously or per os (Coe et al, 2018) or nasal insufflation (Menzies et al, 2019) and C max values ranging from 45.1 to 925 ng/ml plasma and 347.5-517.7 ng/ml plasma, respectively, have been found. Moreover, Menzies et al (2019) have also in vivo demonstrated that RBC cell wall presents no barrier to cocaine and its metabolites, thus corroborating our in vitro studies.…”

“…This conclusion is also supported by two recent studies in which cocaine has been administered intravenously or per os (Coe et al, 2018) or nasal insufflation (Menzies et al, 2019) and C max values ranging from 45.1 to 925 ng/ml plasma and 347.5-517.7 ng/ml plasma, respectively, have been found. Moreover, Menzies et al (2019) have also in vivo demonstrated that RBC cell wall presents no barrier to cocaine and its metabolites, thus corroborating our in vitro studies. Furthermore, since it is known that engineered RBCs produced for clinical use by the "Red Cell Loader" device have a T50 survival approximately of 40 days (Coker et al, 2018), and that the infusion of 160 IU of E196-301 by RBCs is higher than that it is needed to quickly remove all blood cocaine after a single dose intake, it is reasonable to assume that a single infusion can be efficient in blood cocaine degradation both in the case of repeated intakes over time and in the case of higher doses intakes.…”

Blood and Plasma Volumetric Absorptive Microsampling (VAMS) Coupled to LC-MS/MS for the Forensic Assessment of Cocaine Consumption

“…Although some LC-MS/MS methods can be found in the literature in the last few years, dealing with the analysis of COC, BEG, and EME in human plasma [25][26][27][28][29][30][31], only a few of these also include CET [29,30]. Other papers describe COC, BEG, EME [32], and CET [33,34] determination in capillary or venous whole blood.…”

Driving under the influence of cocaine and MDMA: Relationship between blood concentrations and results from clinical test of impairment

“…Menzies et al. ( 28 ) reported a mean blood concentration of 0.34 mg/L following intranasal doses of 100 mg cocaine, with high inter-individual variability, but lower concentrations have also been reported ( 29 ). A common dose of cocaine at “street purity” is 100 – 200 mg ( 5 ), and the purity of cocaine sold in Europe is roughly 60% in many countries ( 3 ).…”