Relationship between cocaine and cocaethylene blood concentration with the severity of clinical manifestations

Zucoloto, Alexandre Dias; Eller, Sarah; Oliveira, Tiago Franco de; Wagner, Gabriela Arantes; Fruchtengarten, Ligia Veras Gimenez; Oliveira, Camila Maria de; Yonamine, Maurı́cio

doi:10.1016/j.ajem.2021.08.057

Cited by 7 publications

(9 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Here, we investigated the impact of ethanol vapor on sample integrity. Cocaine is converted into the cocaethylene metabolite in the presence of ethanol, which has a longer half-life of about 2.5 h. 39 The impact of ethanol vapor on the integrity of the analyte molecules and blood samples was determined through a separate control experiment. The recovery of cocaine and benzoylecgonine in whole blood samples was compared for drug-spiked whole blood samples stored under ambient conditions and ethanolic vapor conditions.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Embossed Paper Platform for Whole Blood Collection, Room Temperature Storage, and Direct Analysis by Pinhole Paper Spray Mass Spectrometry

2022

View full text Add to dashboard Cite

Dry-state microsampling techniques are convenient and advantageous for sample collection in resource-limited settings, including healthcare systems designed for the underserved population. In this work, a microsampling platform based on an embossed hydrophobic paper substrate is introduced together with three-dimensional (3D) printed cartridges that offer opportunities for rapid (<30 min) drying of the collected samples while also preserving sample integrity when the embossed paper chip is shipped at room temperature. More importantly, a new pinhole paper spray ionization method was developed that facilitates direct mass spectrometry (MS) analysis of the dried blood samples without prior sample preparation. We compared the direct pinhole paper spray MS method with a liquid chromatographic (LC) MS approach that relied upon electrospray ionization (ESI) after analytes present in the blood sample were extracted through liquid–liquid extraction. Limits of detection as low as 0.12 and 0.49 ng/mL were calculated for cocaine and its metabolite benzoylecgonine, respectively, when using the direct pinhole paper spray MS method. Analytical merits such as precision and accuracy, recovery, carryover effects, and analyte stability were all quantified for this new paper spray method and compared to the traditional LC-ESI-MS. Although LC-ESI-MS was observed to be 10× more sensitive, the linear dynamic range for both methods was determined to be the same, in the range of 1–500 ng/mL for both cocaine and benzoylecgonine analytes. When fully developed, the current microsampling strategy could offer an easy-to-use kit that can enable a more effective MS analysis of 20 μL dried blood samples delivered by mail. Both sensitivity (10×) and sample stability are found to be more superior for blood prepared in the embossed hydrophobic paper compared to samples prepared in the planar hydrophilic paper.

show abstract

Section: ■ Results and Discussionmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Embossed Paper Platform for Whole Blood Collection, Room Temperature Storage, and Direct Analysis by Pinhole Paper Spray Mass Spectrometry

2022

View full text Add to dashboard Cite

show abstract

“…Instead, the standard target for urine drug testing of cocaine is benzoylecgonine, which also shows a longer detection time than cocaethylene ( Smith et al., 2010 ). Therefore, although cocaethylene may be useful as a risk indicator for combined cocaine and ethanol toxicity and the severity of clinical manifestations ( Wiener et al., 2010 ; Zucoloto et al., 2021 ; Shastry et al., 2022 ), combined urine measurement of benzoylecgonine and EtG/EtS provides similar information in terms of recent use.…”

Section: Discussionmentioning

confidence: 99%

Urine Drug Tests Indicate Higher Prevalence of Combined Alcohol and Cocaine Use Compared to Alcohol Together with Cannabis or Amphetamine—A Possible Link to Cocaethylene

Helander

Villén

Signell

2023

Alcohol and Alcoholism

View full text Add to dashboard Cite

Aim This retrospective study examined the prevalence of combined ethanol and cocaine use, which produces an enhanced psychoactive effect through formation of the active metabolite cocaethylene, compared to combined use of ethanol and two other common recreational drugs, cannabis and amphetamine, based on urine drug test results. Methods The study was based on >30,000 consecutive samples from routine urine drug testing in 2020, and 2627 samples from acute poisonings in the STRIDA project (2010–2016), in Sweden. Drug testing for ethanol (i.e. ethyl glucuronide and ethyl sulfate), cocaine (benzoylecgonine), cannabis (Δ9-THC-COOH) and amphetamine was done by routine immunoassay screening and LC–MS/MS confirmatory methods. Seven samples testing positive for cocaine and ethyl glucuronide were also analyzed for cocaethylene by LC–HRMS/MS. Results Among routine samples for which testing of ethanol and cocaine had been requested, 43% tested positive for both substances, compared with 24% for ethanol and cannabis and 19% for ethanol and amphetamine (P < 0.0001). Among the drug-related intoxications, 60% of cocaine-positive samples were also positive for ethanol, compared to 40% for cannabis and ethanol and 37% for amphetamine and ethanol. Cocaethylene was detected (range 1.3–150 μg/L) in all randomly selected samples testing positive for ethanol and cocaine use. Conclusions These results, which were based on objective laboratory measures, indicated that combined ethanol and cocaine exposure was more prevalent than expected from drug use statistics. This may relate both to the common use of these substances in party and nightlife settings, and the amplified and prolonged pharmacological effect by the active metabolite cocaethylene.

show abstract

“…For example, the single existing (and widely employed) DNA aptamer against cocaine has a modest, ∼5 μM dissociation constant (K D ) 22 and is thus insufficient for monitoring cocaine at clinically relevant concentrations in biological fluids (relevant concentration range: 10−1000 nM). 23,24 In response, we here have utilized a high-stringency, library-immobilized SELEX 25,26 workflow incorporating a rigorous counter-SELEX component 27 to isolate high-affinity DNA aptamers specific against this important target. We then adapted one of the highperformance aptamers into a fluorescent sensor that demonstrated the successful detection of cocaine in serum at clinically relevant concentrations in biological fluids in vitro.…”

Section: ■ Introductionmentioning

confidence: 99%

“…For example, aptamer strand-displacement fluorescence sensors can detect analytes with high sensitivity in biological samples, such as pharmaceuticals and metabolites, with just a single mix-and-read step. − Likewise, electrochemical aptamer-based (EAB) sensors can enable high-frequency, real-time measurement of analytes in the bloodstream, subcutaneous space, and brains of live animals. − The sensitivity and specificity of these sensors, however, are limited by the binding properties of the aptamers they employ. For example, the single existing (and widely employed) DNA aptamer against cocaine has a modest, ∼5 μM dissociation constant ( K D ) and is thus insufficient for monitoring cocaine at clinically relevant concentrations in biological fluids (relevant concentration range: 10–1000 nM). , In response, we here have utilized a high-stringency, library-immobilized SELEX , workflow incorporating a rigorous counter-SELEX component to isolate high-affinity DNA aptamers specific against this important target. We then adapted one of the high-performance aptamers into a fluorescent sensor that demonstrated the successful detection of cocaine in serum at clinically relevant concentrations in biological fluids in vitro .…”

Section: Introductionmentioning

confidence: 99%

High-Affinity Aptamers for In Vitro and In Vivo Cocaine Sensing

Alkhamis,

Canoura,

et al. 2024

J. Am. Chem. Soc.

View full text Add to dashboard Cite

The ability to quantify cocaine in biological fluids is crucial for both the diagnosis of intoxication and overdose in the clinic as well as investigation of the drug's pharmacological and toxicological effects in the laboratory. To this end, we have performed high-stringency in vitro selection to generate DNA aptamers that bind cocaine with nanomolar affinity and clinically relevant specificity, thus representing a dramatic improvement over the current-generation, micromolar-affinity, low-specificity cocaine aptamers. Using these novel aptamers, we then developed two sensors for cocaine detection. The first, an in vitro fluorescent sensor, successfully detects cocaine at clinically relevant levels in 50% human serum without responding significantly to other drugs of abuse, endogenous substances, or a diverse range of therapeutic agents. The second, an electrochemical aptamer-based sensor, supports the real-time, seconds-resolved measurement of cocaine concentrations in vivo in the circulation of live animals. We believe the aptamers and sensors developed here could prove valuable for both point-of-care and on-site clinical cocaine detection as well as fundamental studies of cocaine neuropharmacology.

show abstract

Relationship between cocaine and cocaethylene blood concentration with the severity of clinical manifestations

Cited by 7 publications

References 15 publications

Embossed Paper Platform for Whole Blood Collection, Room Temperature Storage, and Direct Analysis by Pinhole Paper Spray Mass Spectrometry

Embossed Paper Platform for Whole Blood Collection, Room Temperature Storage, and Direct Analysis by Pinhole Paper Spray Mass Spectrometry

Urine Drug Tests Indicate Higher Prevalence of Combined Alcohol and Cocaine Use Compared to Alcohol Together with Cannabis or Amphetamine—A Possible Link to Cocaethylene

High-Affinity Aptamers for In Vitro and In Vivo Cocaine Sensing

Contact Info

Product

Resources

About