The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Andrea Klingmann - One of the best experts on this subject based on the ideXlab platform.
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Application to a Short-Term Degradation Study of Cocaine in Plasma
2016Co-Authors: Andrea Klingmann, Rolf AderjanAbstract:[ Abstract] A method for the determination of cocaine (COC), benzoylEcgonine (BE), Ecgonine methyl ester (EME), and Ecgonine (ECG) in plasma by liquid chromatography-mass spectrometry (LC-MS-MS) was developed. The analytes were isolated from human plasma by subsequent solid-phase extraction and were separated on a Zorbax Eclipse XDB-C8 narrow-bore column using an ammonium acetate buffer/acetonitrile/methanol gradient. A Turbolonspray ~ source was used for ionization. The analytes were characterized by their particular molecular ion a d several fragments. Multiple reaction monitoring (MRM) was used for isolation and quantitation. The assay was rapid, highly sensitive, and reliable. The method was applied to monitor the in vitro degradation of cocaine in plasma. Fresh unpreserved and preserved (0.25 % KF) plasma samples were spiked with 1000 ng cocaine/m/. Aliquots of both series were stored at 4 ~ and 20~ and were analyzed at selected storage times of up to 15 days. In all samples, degradation of cocaine that was dependent on storage time and temperature and on sample preservation could be observed. The formation of BE did not occur to a significant extent (< 12%, referred to the initial concentration of COC), and its concentration was slightly higher in preserved compared with unpreserved plasma at both storage temperatures chosen. EME was formed in considerably higher amounts compared to BE. As already observed for COC, its formation and degradation were dependent on storage time, temperature, and preservation. EME is suggested to be the major source of ECG, which was detectable in all samples after 1-2 days of storage. Although the degradation of COC was shown to be highly dynamic in nature, the sum of all hydrolysis products of COC accounted for the initial COC concentration at any particular time of storage. Therefore, production f * Author to whom correspondence should be addressed
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analysis of cocaine benzoylEcgonine Ecgonine methyl ester and Ecgonine by high pressure liquid chromatography api mass spectrometry and application to a short term degradation study of cocaine in plasma
Journal of Analytical Toxicology, 2001Co-Authors: Andrea Klingmann, Gisela Skopp, Rolf AderjanAbstract:A method for the determination of cocaine (COC), benzoylEcgonine (BE), Ecgonine methyl ester (EME), and Ecgonine (ECG) in plasma by liquid chromatography-mass spectrometry (LC-MS-MS) was developed. The analytes were isolated from human plasma by subsequent solid-phase extraction and were separated on a Zorbax Eclipse XDB-C8 narrow-bore column using an ammonium acetate buffer/acetonitrile/methanol gradient. A Turbolonspray source was used for ionization. The analytes were characterized by their particular molecular ion and several fragments. Multiple reaction monitoring (MRM) was used for isolation and quantitation. The assay was rapid, highly sensitive, and reliable. The method was applied to monitor the in vitro degradation of cocaine in plasma. Fresh unpreserved and preserved (0.25% KF) plasma samples were spiked with 1,000 ng cocaine/mL. Aliquots of both series were stored at 4 degrees C and 20 degrees C and were analyzed at selected storage times of up to 15 days. In all samples, degradation of cocaine that was dependent on storage time and temperature and on sample preservation could be observed. The formation of BE did not occur to a significant extent (< 12%, referred to the initial concentration of COC), and its concentration was slightly higher in preserved compared with unpreserved plasma at both storage temperatures chosen. EME was formed in considerably higher amounts compared to BE. As already observed for COC, its formation and degradation were dependent on storage time, temperature, and preservation. EME is suggested to be the major source of ECG, which was detectable in all samples after 1-2 days of storage. Although the degradation of COC was shown to be highly dynamic in nature, the sum of all hydrolysis products of COC accounted for the initial COC concentration at any particular time of storage. Therefore, production of hitherto unknown degradation products of COC seems unlikely. Moreover, the common transformation product of BE and EME appeared to be stable, and ECG is suggested as a promising postcollection artifact.
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in vitro stability of cocaine in whole blood and plasma including Ecgonine as a target analyte
Therapeutic Drug Monitoring, 2001Co-Authors: Gisela Skopp, Andrea Klingmann, L Potsch, Rainer MatternAbstract:Summary:The in vitro stability of cocaine (COC) was monitored in fresh whole blood and plasma stabilized with potassium fluoride (0.25%) for as long as 15 days. The samples were stored at 4°C, 20°C and 40°C. Additionally, fresh plasma samples containing either benzoylEcgonine (BZE), Ecgonine methyl
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in vitro stability of cocaine in whole blood and plasma including Ecgonine as a target analyte
Therapeutic Drug Monitoring, 2001Co-Authors: Gisela Skopp, Andrea Klingmann, L Potsch, Rainer MatternAbstract:The in vitro stability of cocaine (COC) was monitored in fresh whole blood and plasma stabilized with potassium fluoride (0.25%) for as long as 15 days. The samples were stored at 4 degreesC, 20 degreesC and 40 degreesC. Additionally, fresh plasma samples containing either benzoylEcgonine (BZE), Ecgonine methyl ester (EME) or Ecgonine (ECG) were stored at 4 degreesC and 20 degreesC. Data were established using subsequent solid-phase extraction procedures and high-performance liquid chromatography coupled to atmospheric pressure ionization mass spectrometry for isolation and quantitation of COC, BZE, EME, and ECG. COC, BZE, and EME concentrations decreased with increasing storage temperature and time after an apparent first-order reaction kinetic. Only ECG appeared to be stable at storage temperatures as high as 20 degreesC for the entire observation period. At 40 degreesC, the amount of ECG produced from hydrolysis of COC still totalled 80% of the initial COC concentration. Hydrolysis of COC to EME occurred more rapidly in plasma than in blood. The dynamic degradation profiles obtained were dependent on the storage temperature. The conversion of COC to BZE, EME, and ECG appeared to be stoichiometric at all time intervals at storage temperatures of 4 degreesC and 20 degreesC. The presence of any hydrolysis product of COC in blood or plasma constitutes confirmatory evidence of COC incorporation, and determination of ECG seems most promising even in samples stored under unfavorable conditions.
Rolf Aderjan - One of the best experts on this subject based on the ideXlab platform.
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Application to a Short-Term Degradation Study of Cocaine in Plasma
2016Co-Authors: Andrea Klingmann, Rolf AderjanAbstract:[ Abstract] A method for the determination of cocaine (COC), benzoylEcgonine (BE), Ecgonine methyl ester (EME), and Ecgonine (ECG) in plasma by liquid chromatography-mass spectrometry (LC-MS-MS) was developed. The analytes were isolated from human plasma by subsequent solid-phase extraction and were separated on a Zorbax Eclipse XDB-C8 narrow-bore column using an ammonium acetate buffer/acetonitrile/methanol gradient. A Turbolonspray ~ source was used for ionization. The analytes were characterized by their particular molecular ion a d several fragments. Multiple reaction monitoring (MRM) was used for isolation and quantitation. The assay was rapid, highly sensitive, and reliable. The method was applied to monitor the in vitro degradation of cocaine in plasma. Fresh unpreserved and preserved (0.25 % KF) plasma samples were spiked with 1000 ng cocaine/m/. Aliquots of both series were stored at 4 ~ and 20~ and were analyzed at selected storage times of up to 15 days. In all samples, degradation of cocaine that was dependent on storage time and temperature and on sample preservation could be observed. The formation of BE did not occur to a significant extent (< 12%, referred to the initial concentration of COC), and its concentration was slightly higher in preserved compared with unpreserved plasma at both storage temperatures chosen. EME was formed in considerably higher amounts compared to BE. As already observed for COC, its formation and degradation were dependent on storage time, temperature, and preservation. EME is suggested to be the major source of ECG, which was detectable in all samples after 1-2 days of storage. Although the degradation of COC was shown to be highly dynamic in nature, the sum of all hydrolysis products of COC accounted for the initial COC concentration at any particular time of storage. Therefore, production f * Author to whom correspondence should be addressed
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analysis of cocaine benzoylEcgonine Ecgonine methyl ester and Ecgonine by high pressure liquid chromatography api mass spectrometry and application to a short term degradation study of cocaine in plasma
Journal of Analytical Toxicology, 2001Co-Authors: Andrea Klingmann, Gisela Skopp, Rolf AderjanAbstract:A method for the determination of cocaine (COC), benzoylEcgonine (BE), Ecgonine methyl ester (EME), and Ecgonine (ECG) in plasma by liquid chromatography-mass spectrometry (LC-MS-MS) was developed. The analytes were isolated from human plasma by subsequent solid-phase extraction and were separated on a Zorbax Eclipse XDB-C8 narrow-bore column using an ammonium acetate buffer/acetonitrile/methanol gradient. A Turbolonspray source was used for ionization. The analytes were characterized by their particular molecular ion and several fragments. Multiple reaction monitoring (MRM) was used for isolation and quantitation. The assay was rapid, highly sensitive, and reliable. The method was applied to monitor the in vitro degradation of cocaine in plasma. Fresh unpreserved and preserved (0.25% KF) plasma samples were spiked with 1,000 ng cocaine/mL. Aliquots of both series were stored at 4 degrees C and 20 degrees C and were analyzed at selected storage times of up to 15 days. In all samples, degradation of cocaine that was dependent on storage time and temperature and on sample preservation could be observed. The formation of BE did not occur to a significant extent (< 12%, referred to the initial concentration of COC), and its concentration was slightly higher in preserved compared with unpreserved plasma at both storage temperatures chosen. EME was formed in considerably higher amounts compared to BE. As already observed for COC, its formation and degradation were dependent on storage time, temperature, and preservation. EME is suggested to be the major source of ECG, which was detectable in all samples after 1-2 days of storage. Although the degradation of COC was shown to be highly dynamic in nature, the sum of all hydrolysis products of COC accounted for the initial COC concentration at any particular time of storage. Therefore, production of hitherto unknown degradation products of COC seems unlikely. Moreover, the common transformation product of BE and EME appeared to be stable, and ECG is suggested as a promising postcollection artifact.
Gisela Skopp - One of the best experts on this subject based on the ideXlab platform.
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analysis of cocaine benzoylEcgonine Ecgonine methyl ester and Ecgonine by high pressure liquid chromatography api mass spectrometry and application to a short term degradation study of cocaine in plasma
Journal of Analytical Toxicology, 2001Co-Authors: Andrea Klingmann, Gisela Skopp, Rolf AderjanAbstract:A method for the determination of cocaine (COC), benzoylEcgonine (BE), Ecgonine methyl ester (EME), and Ecgonine (ECG) in plasma by liquid chromatography-mass spectrometry (LC-MS-MS) was developed. The analytes were isolated from human plasma by subsequent solid-phase extraction and were separated on a Zorbax Eclipse XDB-C8 narrow-bore column using an ammonium acetate buffer/acetonitrile/methanol gradient. A Turbolonspray source was used for ionization. The analytes were characterized by their particular molecular ion and several fragments. Multiple reaction monitoring (MRM) was used for isolation and quantitation. The assay was rapid, highly sensitive, and reliable. The method was applied to monitor the in vitro degradation of cocaine in plasma. Fresh unpreserved and preserved (0.25% KF) plasma samples were spiked with 1,000 ng cocaine/mL. Aliquots of both series were stored at 4 degrees C and 20 degrees C and were analyzed at selected storage times of up to 15 days. In all samples, degradation of cocaine that was dependent on storage time and temperature and on sample preservation could be observed. The formation of BE did not occur to a significant extent (< 12%, referred to the initial concentration of COC), and its concentration was slightly higher in preserved compared with unpreserved plasma at both storage temperatures chosen. EME was formed in considerably higher amounts compared to BE. As already observed for COC, its formation and degradation were dependent on storage time, temperature, and preservation. EME is suggested to be the major source of ECG, which was detectable in all samples after 1-2 days of storage. Although the degradation of COC was shown to be highly dynamic in nature, the sum of all hydrolysis products of COC accounted for the initial COC concentration at any particular time of storage. Therefore, production of hitherto unknown degradation products of COC seems unlikely. Moreover, the common transformation product of BE and EME appeared to be stable, and ECG is suggested as a promising postcollection artifact.
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in vitro stability of cocaine in whole blood and plasma including Ecgonine as a target analyte
Therapeutic Drug Monitoring, 2001Co-Authors: Gisela Skopp, Andrea Klingmann, L Potsch, Rainer MatternAbstract:Summary:The in vitro stability of cocaine (COC) was monitored in fresh whole blood and plasma stabilized with potassium fluoride (0.25%) for as long as 15 days. The samples were stored at 4°C, 20°C and 40°C. Additionally, fresh plasma samples containing either benzoylEcgonine (BZE), Ecgonine methyl
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in vitro stability of cocaine in whole blood and plasma including Ecgonine as a target analyte
Therapeutic Drug Monitoring, 2001Co-Authors: Gisela Skopp, Andrea Klingmann, L Potsch, Rainer MatternAbstract:The in vitro stability of cocaine (COC) was monitored in fresh whole blood and plasma stabilized with potassium fluoride (0.25%) for as long as 15 days. The samples were stored at 4 degreesC, 20 degreesC and 40 degreesC. Additionally, fresh plasma samples containing either benzoylEcgonine (BZE), Ecgonine methyl ester (EME) or Ecgonine (ECG) were stored at 4 degreesC and 20 degreesC. Data were established using subsequent solid-phase extraction procedures and high-performance liquid chromatography coupled to atmospheric pressure ionization mass spectrometry for isolation and quantitation of COC, BZE, EME, and ECG. COC, BZE, and EME concentrations decreased with increasing storage temperature and time after an apparent first-order reaction kinetic. Only ECG appeared to be stable at storage temperatures as high as 20 degreesC for the entire observation period. At 40 degreesC, the amount of ECG produced from hydrolysis of COC still totalled 80% of the initial COC concentration. Hydrolysis of COC to EME occurred more rapidly in plasma than in blood. The dynamic degradation profiles obtained were dependent on the storage temperature. The conversion of COC to BZE, EME, and ECG appeared to be stoichiometric at all time intervals at storage temperatures of 4 degreesC and 20 degreesC. The presence of any hydrolysis product of COC in blood or plasma constitutes confirmatory evidence of COC incorporation, and determination of ECG seems most promising even in samples stored under unfavorable conditions.
Berend Mets - One of the best experts on this subject based on the ideXlab platform.
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Chronic continuous cocaine infusion in rats: Effect on urine cocaine, Ecgonine methylester and benzoylEcgonine concentrations and bolus-dose cocaine pharmacokinetics
Journal of Pharmacy and Pharmacology, 2000Co-Authors: Berend Mets, E. Soo, J. Diaz, C. B. Pantuck, G. Singh, I. A. BlairAbstract:The aim of this study was to determine the effect of chronic cocaine infusion on urine cocaine, Ecgonine methylester and benzoylEcgonine concentrations to establish if they varied with dose and duration of cocaine administration. Male rats were continuously infused with cocaine at either 6 or 18 mg kg(-1) daily for 13 days. Three urine samples taken over the course of the infusion period showed that cocaine, Ecgonine methylester and benzoylEcgonine concentrations varied with the dose administered and the duration of administration. Cocaine, Ecgonine methylester and benzoylEcgonine concentrations were 2-3 times greater in the high-dose group than the low-dose group at each sampling time point. These decreased, respectively, from 7.0+/-1.1, 26.7+/-4.5 and 29.5+/-5.4 microg mL(-1) to 2.5+/-0.5, 10.5+/-1.8 and 11.8+/-1.5 microg mL(-1) in the high-dose group and from 1.0+/-0-2, 7.8+/-1.5 and 6.3+/-0.1 microg mL(-1) to 0.5+/-0.1, 4.0+/-0.6 and 3.1+/-0.4 microg mL(-1) in the low-dose group (P 0.05)). We conclude that chronic cocaine infusion does not alter cocaine metabolism. This was not reflected by absolute cocaine metabolite urine concentrations, which varied with time, but was represented by urine Ecgonine methyl ester/benzoylEcgonine concentration ratios.
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Cocaine, norcocaine, Ecgonine methylester and benzoylEcgonine pharmacokinetics in the rat
Life Sciences, 1999Co-Authors: Berend Mets, E. Soo, J. Diaz, Subhash C. JamdarAbstract:Abstract We have compared the pharmacokinetics of bolus dose cocaine administration with that of its three most important metabolites; norcocaine, Ecgonine methylester, and benzoylEcgonine and assessed whether kinetics are dose dependent at two equimolar doses equivalent to cocaine hydrochloride 2.5 and 5 mg kg respectively. Forty-nine male Sprague-Dawley rats were randomly divided into 8 groups to receive iv either high (14.7 umol kg ) (HI) or low (7.3 umol kg ) (LO) bolus doses of cocaine or one of its metabolites. Arterial blood samples for cocaine and metabolite analysis were taken repetitively over the next 3 h. Equimolar bolus doses of these congeners showed biexponential plasma concentration decay curves which were fitted to a two compartment model and subjected to noncompartmental analysis. The plasma concentration time profiles were significantly different for the HI and LO doses administered for each congener. The elimination half-lives of cocaine and norcocaine were similar (28–33 min), that for Ecgonine methylester (60–71 min) was approximately twice this and for benzoylEcgonine was 40–44 min. Cocaine clearance (155–158 ml/kg/min) was found to be in the range found in other rat studies. Ecgonine methylester clearance and benzoylEcgonine clearance were found to be one quarter and one eighth of this value respectively. The pharmacokinetic profile of these congeners was not dose dependent when the two doses administered were compared.
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A validated stable isotope dilution liquid chromatography tandem mass spectrometry assay for the trace analysis of cocaine and its major metabolites in plasma.
Analytical Chemistry, 1999Co-Authors: G. Singh, Berend Mets, V. Arora, P. T. Fenn, Ian A. BlairAbstract:A validated method has been developed for the simultaneous quantitation of cocaine and its major metabolites (Ecgonine methyl ester, benzoylEcgonine, and norcocaine) in rat plasma. The method is based upon the use of stable isotope dilution liquid chromatography/atmospheric pressure chemical ionization/tandem mass spectrometry. Previously reported methods do not have the sensitivity and specificity that can be attained with this method. Plasma samples required no cleanup apart from protein precipitation, and no derivatization was required. Selected reaction monitoring was performed on the transitions of m/z 200 to m/z 182 (Ecgonine methyl ester), m/z 290 to m/z 168 (benzoylEcgonine), m/z 304 to m/z 182 (cocaine), and m/z 290 to m/z 168 (norcocaine). The standard curves were linear over the range from 2 ng/mL (benzoylEcgonine, cocaine, and norcocaine) or 5 ng/mL (Ecgonine methyl ester) to 1000 ng/mL in rat plasma. The lower limit of quantitation (LLQ) for benzoylEcgonine, cocaine, and norcocaine was 2 ng/m...
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a catalytic antibody against cocaine prevents cocaine s reinforcing and toxic effects in rats
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: Berend Mets, Subhash C. Jamdar, Gail Winger, Camilo L Cabrera, Susan K Seo, Ginger Yang, Kang Zhao, Richard J Briscoe, Rowena Almonte, James H WoodsAbstract:Cocaine addiction and overdose have long defied specific treatment. To provide a new approach, the high-activity catalytic antibody mAb 15A10 was elicited using a transition-state analog for the hydrolysis of cocaine to nontoxic, nonaddictive products. In a model of cocaine overdose, mAb 15A10 protected rats from cocaine-induced seizures and sudden death in a dose-dependent fashion; a noncatalytic anticocaine antibody did not reduce toxicity. Consistent with accelerated catalysis, the hydrolysis product Ecgonine methyl ester was increased >10-fold in plasma of rats receiving mAb 15A10 and lethal amounts of cocaine. In a model of cocaine addiction, mAb 15A10 blocked completely the reinforcing effect of cocaine in rats. mAb 15A10 blocked cocaine specifically and did not affect behavior maintained by milk or by the dopamine reuptake inhibitor bupropion. This artificial cocaine esterase is a rationally designed cocaine antagonist and a catalytic antibody with potential for medicinal use.
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determination of cocaine norcocaine benzoylEcgonine and Ecgonine methyl ester in rat plasma by high performance liquid chromatography with ultraviolet detection
Journal of Chromatography B: Biomedical Sciences and Applications, 1996Co-Authors: Laszlo Virag, Berend Mets, Subhash C. JamdarAbstract:An isocratic high-performance liquid chromatographic method with ultraviolet detection at 235 nm is described for the determination of cocaine and its metabolites benzoylEcgonine, norcocaine and Ecgonine methyl ester in rat plasma, collected during toxicity studies. Following simultaneous solid-phase extraction of all analytes and the internal standard tropacocaine, cocaine, benzoylEcgonine and norcocaine were separated on a C18 column. Ecgonine methyl ester and cocaine were separated on coupled cyanopropyl and silica columns, following derivatization of Ecgonine methyl ester to p-fluorococaine. The extraction efficiencies of these compounds from plasma ranged from 78 to 87%, while the limits of detection ranged from 35 to 90 ng/ml. The assay was linear from 300 to 5000 ng/ml, and the within-day precision 2 to 8% over this concentration range.
Edward J Cone - One of the best experts on this subject based on the ideXlab platform.
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urinary excretion of Ecgonine and five other cocaine metabolites following controlled oral intravenous intranasal and smoked administration of cocaine
Journal of Analytical Toxicology, 2010Co-Authors: Michael L Smith, Edward J Cone, Eric T Shimomura, Buddha D Paul, David W Darwin, Marilyn A HuestisAbstract:Urinary excretion of Ecgonine (EC) was compared to that of cocaine, benzoylEcgonine, Ecgonine methyl ester and minor metabolites, meta-hydroxybenzoylEcgonine, para-hydroxybenzoylEcgonine, and norbenzoylEcgonine, following controlled administration of oral, intravenous, intranasal, and smoked cocaine. Urine EC concentrations peaked later than all other analytes and had longer detection times than the other minor metabolites. With a 50 ng/mL cutoff concentration and following low doses of 10 to 45 mg cocaine by multiple routes, detection times extended up to 98 h. Maximum concentrations (Cmax) were 6-14 mole % of those for benzoylEcgonine, Cmax increased with dose, time to maximum concentration (Tmax) was independent of dose, and route of administration did not have a significant impact on Cmax or Tmax for metabolites. EC is an analyte to consider for identifying cocaine use due to its stability in urine and long detection times.
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simultaneous measurement of cocaine cocaethylene their metabolites and crack pyrolysis products by gas chromatography mass spectrometry
Clinical Chemistry, 1994Co-Authors: Edward J Cone, Mary Hillsgrove, William D DarwinAbstract:We developed a sensitive and specific assay for the simultaneous measurement of cocaine, cocaethylene, six of their metabolites, and anhydroEcgonine methyl ester, a pyrolysis product, in biological fluids. The assay involves solid-phase extraction columns containing a copolymeric bonded phase for isolation of cocaine analytes, derivatization with N,O-bis(trimethylsilyl)trifluoroacetamide and 10 g/L trimethylchlorosilane, and measurement with gas chromatography-mass spectrometry operating in the selected-ion monitoring mode. Detector responses for analytes were linear over a concentration range of 3.1-1000 micrograms/L. The limits of detection were approximately 1 microgram/L for cocaine, Ecgonine methyl ester, and benzoylEcgonine and 3-6 micrograms/L for the remaining analytes. Hydrolysis of cocaine and artifact formation of anhydroecogonine methyl ester during extraction and assay was < 1%. Cocaine and its derivatives appear in different proportions in plasma, saliva, and urine according to the biological fluid and time of measurement. Each biological fluid provides unique information on the disposition of cocaine in human subjects.
