Determination of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, 2-ethyl-5-methyl-3,3-diphenylpyraline and methadol in meconium by liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry

Choo, Robin E.; Murphy, Constance M.; Jones, Hendrée E.; Huestis, Marilyn A.

doi:10.1016/j.jchromb.2004.10.068

Cited by 42 publications

(25 citation statements)

References 22 publications

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“…The primary application of LC/MS was to identify original compounds and their metabolites with ion peaks and fragments. However, this method is now being applied by many investigators to identify trace levels in biological fluids (Choo et al, 2005). The basis of pharmacokinetic calculation consists of compartment and noncompartment models, of which the former is considered limited because the influence of drug and metabolite distribution in the body on concentration-time curves is often neglected (Weiss, 1988).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Berberine and Its Main Metabolites in Conventional and Pseudo Germ-Free Rats Determined by Liquid Chromatography/Ion Trap Mass Spectrometry

Zuo

Nakamura²,

Akao³

et al. 2006

Drug Metab Dispos

253

153

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ABSTRACT:Berberine (Ber) and its main metabolites were identified and quantified using liquid chromatography/electrospray ionization/ion trap mass spectrometry. Rat plasma contained the main metabolites, berberrubine, thalifendine, demethyleneberberine, and jatrorrhizine, as free and glucuronide conjugates after p.o. Ber administration. Moreover, the original drug, the four main metabolites, and their glucuronide conjugates were all detected in liver tissues after 0.5 h and in bile samples 1 h after p.o. Ber administration. Therefore, the metabolic site seemed to be the liver, and the metabolites and conjugates were evidently excreted into the duodenum as bile. The pharmacokinetics of Ber and the four metabolites were determined in conventional and pseudo germ-free rats (treated with antibiotics) after p.o. administration with 40 mg/kg Ber. The AUC 0-limt and mean transit time values of the metabolites significantly differed between conventional and pseudo germ-free rats. The amounts of metabolites were remarkably reduced in the pseudo germ-free rats, whereas levels of Ber did not obviously differ between the two groups. The intestinal flora did not exert significant metabolic activity against Ber and its metabolites, but it played a significant role in the enterohepatic circulation of metabolites. In this sense, the liver and intestinal bacteria participate in the metabolism and disposition of Ber in vivo.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Berberine and Its Main Metabolites in Conventional and Pseudo Germ-Free Rats Determined by Liquid Chromatography/Ion Trap Mass Spectrometry

Zuo

Nakamura²,

Akao³

et al. 2006

Drug Metab Dispos

253

153

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“…APCI is a more harsh ionization technique, and it may cause the compounds to break down in ion source. It is often used for enhanced ionization of neutral compounds, for larger dynamic range, and to overcome the matrix effects [35] .…”

Section: Ionization Techniquesmentioning

confidence: 99%

LC‐MS in Drug Metabolism and Pharmacokinetics: A Pharmaceutical Industry Perspective

Jian

Shou

Edom

et al. 2012

Mass Spectrometry Handbook

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“…EDDP has been identified as a metabolite in tissues, plasma, urine, and hair [6][7][8][9]. A second metabolite (2-ethyl-5-methyl-3, 3-diphenylpyrroline, EMDP) is formed either by further demethylation of the secondary amine, prior to cyclization, or from EDDP after cyclization [10].…”

Section: Introductionmentioning

confidence: 99%

“…For example, Alburges et al [7] observed that EDDP concentrations in plasma were generally less than 10% of METH concentrations and EMDP either was not detected or was present only at concentrations below 10 ng/ml. More recently, liquid chromatographic/tandem mass spectrometric (LC/MS/MS) procedures have been applied and small amounts of EMDP have been reported in meconium or plasma from infants after maternal exposure to methadone [8,9].…”

Section: Introductionmentioning

confidence: 99%

Methadone and methadone metabolites in postmortem specimens

Danielson¹,

Mozayani²,

Sánchez³

2008

Forensic Sci Med Pathol

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We have determined drug/metabolite concentrations and ratios of methadone (METH) to two of its metabolites (EDDP, 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine; and EMDP, 2-ethyl-5-methyl-3,3-diphenylpyrroline) in postmortem peripheral blood and liver tissue by liquid chromatography/tandem mass spectrometry. The assays employed deuterated internal standards and multiple reaction monitoring (MRM) techniques. The assay linear range was 0.01-2.0 mg/l for each analyte. METH, EDDP, and EMDP were determined in liver and peripheral blood from 46 methadone-positive cases. METH and EDDP were detected in all specimens, whether blood or liver. EMDP was detected, only in liver, and only 17 cases, at concentrations much lower than those of EDDP. Concentrations of METH and EDDP in blood and liver from EMDP-positive cases were in ranges higher than, but overlapping with, concentrations in blood and liver from EMDP-negative cases. These data suggest that although METH is readily demethylated and cyclized to EDDP, in vivo, conversion to EMDP may be less efficient and its accumulation in postmortem tissues may be highly individual.

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Determination of methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, 2-ethyl-5-methyl-3,3-diphenylpyraline and methadol in meconium by liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry

Cited by 42 publications

References 22 publications

Pharmacokinetics of Berberine and Its Main Metabolites in Conventional and Pseudo Germ-Free Rats Determined by Liquid Chromatography/Ion Trap Mass Spectrometry

Pharmacokinetics of Berberine and Its Main Metabolites in Conventional and Pseudo Germ-Free Rats Determined by Liquid Chromatography/Ion Trap Mass Spectrometry

LC‐MS in Drug Metabolism and Pharmacokinetics: A Pharmaceutical Industry Perspective

Methadone and methadone metabolites in postmortem specimens

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