Cocaine and Metabolite Concentrations in DBS and Venous Blood After Controlled Intravenous Cocaine Administration

Ellefsen, Kayla N.; Costa, José Luiz; Concheiro, Marta; Anizan, Sébastien; Barnes, Allan J.; Pirard, Sandrine; Gorelick, David A.; Huestis, Marilyn A.

doi:10.4155/bio.15.127

Cited by 23 publications

(25 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…16 The authors observed an enhanced stability of the studied substances in DBS compared to that on blood stored at the same temperature. In fact, several times a toxicological evaluation of a case may be requested by the Prosecutor even several days or weeks after autopsy and sample collection.…”

mentioning

confidence: 90%

“…The major problem related to forensic analyses is the interpretation of quantitative results. 16 They obtained good qualitative correlation between DBS and venous blood, while DBS provided much higher scattering in quantitative results. Normally, blood is deposed on a specific paper substrate, is allowed to dry and eventually a small portion (2-7 mm) of filter is removed and extracted.…”

mentioning

confidence: 96%

See 1 more Smart Citation

A liquid chromatography–tandem mass spectrometry method for the determination of cocaine and metabolites in blood and in dried blood spots collected from postmortem samples and evaluation of the stability over a 3‐month period

Moretti

Visonà

Freni

et al. 2018

Drug Testing and Analysis

View full text Add to dashboard Cite

The aims of this study were (1) to identify and quantify cocaine (COC), benzoylecgonine (BE), ecgonine methyl ester (EME), and cocaethylene (CE) in DBS; (2) to compare dried blood spots (DBSs) analytical results with the routine blood analyses; (3) to monitor analytes stability on DBS within a 3-month period. Eighty-five μL of blood from postmortem cases were put on a card for DBS analysis and kept in the dark, at room temperature. Samples were extracted through solid-phase extraction (SPE) cartridges and injected in the liquid chromatography-tandem mass spectrometry (LC-MS/MS) system. The analytical procedure is simple, sensitive, and specific. Limits of detection (LODs) and quantification (LOQs) were calculated at 1.0 and 5.0 ng/mL(g) for COC and CE, and at 0.5 and 2 ng/mL for EME and BE, respectively. Validation parameters fulfilled all the acceptance criteria. Fifty-five postmortem cases were evaluated. Eighteen cases were positive for COC (44-2456 ng/mL) and BE (228-4700 ng/mL), 12 for EME (92-1500 ng/mL), and 11 cases for CE (11-273 ng/mL). Stability was evaluated on 8 cases collected in the period January 2017-January 2018. For each case, 5 DBSs were collected at T0. Four DBSs were analyzed within the 4 following weeks and 1 sample was analyzed after 3 months. The concentrations on DBSs, stored at room temperature, always matched the ones obtained on blood samples kept at -20°C (<20% variation, both at T0 and after 3 months). BE and COC concentrations remained stable after a 3-month storage, EME concentrations slightly increased after 3 weeks in the 2 analyzed samples, while CE provided a less homogeneous stability depending on the sample.

show abstract

mentioning

confidence: 90%

mentioning

confidence: 96%

A liquid chromatography–tandem mass spectrometry method for the determination of cocaine and metabolites in blood and in dried blood spots collected from postmortem samples and evaluation of the stability over a 3‐month period

Moretti

Visonà

Freni

et al. 2018

Drug Testing and Analysis

View full text Add to dashboard Cite

show abstract

“…Cocaine and BE OF were quantified with modifications of a previously validated venous blood analytical method [28]. Calibrators were prepared at drug concentrations from 1–100 μg/L in 0.75 mL (OE: 0.25 mL blank OF + 0.5 mL OE stabilizing buffer) or 0.5 mL (SS: 0.25 mL blank OF + 0.25 mL SS buffer) solutions at the same dilutions as authentic specimens, therefore, accounting for the dilution factor.…”

Section: Methodsmentioning

confidence: 99%

“…After evaporating to dryness, samples were derivatized with 20 μL ethyl acetate:MTBSTFA + 1% t-BDMS (50:50 v/v) for 40 min at 70°C. The derivatized extracts (2 μL) were analyzed by an electron impact two-dimensional (2D) GC-MS method [28] with oven temperature program modifications for a total run time of 18.05 min (Supplemental Table 1). Instrument parameters were described in detail previously [28] and are outlined in Supplemental Table 1.…”

Section: Methodsmentioning

confidence: 99%

“…The derivatized extracts (2 μL) were analyzed by an electron impact two-dimensional (2D) GC-MS method [28] with oven temperature program modifications for a total run time of 18.05 min (Supplemental Table 1). Instrument parameters were described in detail previously [28] and are outlined in Supplemental Table 1. The upper limit of linearity was 100 μg/L; specimens exceeding this limit were diluted with oral fluid and buffer mixture (2:1, v/v; 1:1 v/v), re-extracted and analyzed.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Oral fluid cocaine and benzoylecgonine concentrations following controlled intravenous cocaine administration

Ellefsen

Concheiro

Pirard

et al. 2016

Forensic Science International

Self Cite

View full text Add to dashboard Cite

Limited oral fluid (OF) pharmacokinetic data collected with commercially available collection devices after controlled cocaine administration hinder OF result interpretations. Ten cocaine-using adults provided OF, collected with Oral-Eze® (OE) and StatSure Saliva Sampler™ (SS) devices, an hour prior to and up to 69 h after 25 mg intravenous (IV) cocaine administration. Cocaine and benzoylecgonine (BE) were quantified by a validated 2D-GC-MS method. Large inter-subject variability was observed. Cocaine was detected in OF in the first 0.17 h sample after IV administration, with much more rapid elimination than BE. OE median observed Cmax (range) was 932 (394–1,574) μg/L for cocaine and 248 (96.9–953) μg/L for BE. SS median (range) observed cocaine and BE Cmax trended lower at 732 (83.3–1,892) μg/L and 360 (77.2–836) μg/L, respectively. OE and SS cocaine OF detection times were 12.5 and 6.5 h and for BE 30.5 and 28.0 h, respectively at 1 μg/L. There were no significant pharmacokinetic differences between OE and SS OF collection devices, except cocaine half-life was significantly shorter in SS OF specimens. This difference could be attributed to differences in stabilizing buffers present in OF collection devices, which may affect cocaine stability in OF specimens, or decreased recovery from collection pads. Both OE and SS OF collection devices were effective in monitoring cocaine and metabolite concentrations with similar detection windows. Furthermore, we demonstrated that different confirmatory OF cutoffs can be selected to produce shorter or longer cocaine and metabolite detection windows to address specific needs of clinical and forensic drug testing programs.

show abstract

Quantification of cocaine and cocaine metabolites in dried blood spots from a controlled administration study using liquid chromatography–tandem mass spectrometry

Ambach

Menzies

Parkin

et al. 2018

Drug Testing and Analysis

View full text Add to dashboard Cite

Cocaine is a common illicit stimulant and is mainly metabolized by hydrolysis to benzoylecgonine (BE) and ecgonine methyl ester (EME), but also to minor metabolites like norcocaine, or hydroxy-BE. When ethanol is present, cocaethylene is formed.Dried blood spot (DBS) sampling is a minimally invasive microsampling technique with possible advantages for analyte stability and ease of storage, making it an attractive matrix in forensic and clinical settings. We developed a liquid chromatographytandem mass spectrometry-based (LC-MS/MS) method for quantifying cocaine, BE, EME, norcocaine, hydroxy-BE, and cocaethylene in DBS. Six-mm punches were extracted with aqueous buffer followed by protein precipitation, evaporation and reconstitution in mobile phase. Separation was achieved on a Polar-RP column (Phenomenex) in a 6-minute gradient including baseline-separation of norcocaine and BE. For MS detection, a QTRAP 5500 (Sciex) was used in positive electrospray ionization (ESI) multiple reaction monitoring (MRM) mode. The method was validated for selectivity, sensitivity [lower limited of quantification (LLOQ) 1.0-5.0 ng/mL], imprecision (≤13.4%, ≤19.6% at LLOQ), accuracy (≤ ± 14.9%), matrix effects, extraction efficiency (≥20.9%), hematocrit effect, volume spotted, punch location, longterm and autosampler stability. Concentrations in DBS from a controlled cocaine administration study in healthy volunteers were compared to whole blood and plasma. Although concentrations correlated moderately to strongly (Spearman's ρ 0.603-0.958), agreement between paired samples was poor, with overestimation of DBS concentrations and wide confidence intervals in Bland-Altman analysis. A possible cause are differences in capillary and venous blood concentrations, with the underlying mechanism requiring further research before DBS analysis for cocaine and its metabolites can be considered equivalent to whole blood or plasma analysis.

show abstract

Cocaine and Metabolite Concentrations in DBS and Venous Blood After Controlled Intravenous Cocaine Administration

Cited by 23 publications

References 44 publications

A liquid chromatography–tandem mass spectrometry method for the determination of cocaine and metabolites in blood and in dried blood spots collected from postmortem samples and evaluation of the stability over a 3‐month period

A liquid chromatography–tandem mass spectrometry method for the determination of cocaine and metabolites in blood and in dried blood spots collected from postmortem samples and evaluation of the stability over a 3‐month period

Oral fluid cocaine and benzoylecgonine concentrations following controlled intravenous cocaine administration

Quantification of cocaine and cocaine metabolites in dried blood spots from a controlled administration study using liquid chromatography–tandem mass spectrometry

Contact Info

Product

Resources

About