The Experts below are selected from a list of 48 Experts worldwide ranked by ideXlab platform
Neal L. Benowitz - One of the best experts on this subject based on the ideXlab platform.
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A clinical pharmacological study of subcutaneous nicotine
European Journal of Clinical Pharmacology, 1993Co-Authors: J. Le Houezec, P. Jacob, Neal L. BenowitzAbstract:The stable Isotope-Labeled Compound 3',-3'-dideuteronicotine (nicotine-d_2) was used to investigate the disposition kinetics and effects of nicotine administered subcutaneously to 6 smokers. Plasma nicotine-d_2 concentrations were measured for 8 h after subcutaneous injection of 4 doses (0.4, 0.8, 1.2, and 2.4 mg). Peak plasma nicotine concentration correlated well with the dose, averaging 2.8 to 14.8 ng/ml, 19 to 25 min after injection of the 0.4 mg and 2.4 mg doses, respectively. The plasma clearance over bioavailability ratio (CL/f) averaged 12 to 13 ml · min^−1 · kg^−1, similar to the clearance reported previously for intravenously administered nicotine. Thus, bioavailability appears to be approximately 100%. The heart rate response was more sensitive to the nicotine dose than the blood pressure response. Subjective effects showed large interindividual variability. The results reported herein may be useful in planning future studies. Administration of nicotine by the subcutaneous route appears to be a practical and safe method for studying the human pharmacology of nicotine.
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A clinical pharmacological study of subcutaneous nicotine
European journal of clinical pharmacology, 1993Co-Authors: J. Le Houezec, P. Jacob, Neal L. BenowitzAbstract:The stable Isotope-Labeled Compound 3',-3'-dideuteronicotine (nicotine-d2) was used to investigate the disposition kinetics and effects of nicotine administered subcutaneously to 6 smokers. Plasma nicotine-d2 concentrations were measured for 8 h after subcutaneous injection of 4 doses (0.4, 0.8, 1.2, and 2.4 mg).
J. Le Houezec - One of the best experts on this subject based on the ideXlab platform.
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A clinical pharmacological study of subcutaneous nicotine
European Journal of Clinical Pharmacology, 1993Co-Authors: J. Le Houezec, P. Jacob, Neal L. BenowitzAbstract:The stable Isotope-Labeled Compound 3',-3'-dideuteronicotine (nicotine-d_2) was used to investigate the disposition kinetics and effects of nicotine administered subcutaneously to 6 smokers. Plasma nicotine-d_2 concentrations were measured for 8 h after subcutaneous injection of 4 doses (0.4, 0.8, 1.2, and 2.4 mg). Peak plasma nicotine concentration correlated well with the dose, averaging 2.8 to 14.8 ng/ml, 19 to 25 min after injection of the 0.4 mg and 2.4 mg doses, respectively. The plasma clearance over bioavailability ratio (CL/f) averaged 12 to 13 ml · min^−1 · kg^−1, similar to the clearance reported previously for intravenously administered nicotine. Thus, bioavailability appears to be approximately 100%. The heart rate response was more sensitive to the nicotine dose than the blood pressure response. Subjective effects showed large interindividual variability. The results reported herein may be useful in planning future studies. Administration of nicotine by the subcutaneous route appears to be a practical and safe method for studying the human pharmacology of nicotine.
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A clinical pharmacological study of subcutaneous nicotine
European journal of clinical pharmacology, 1993Co-Authors: J. Le Houezec, P. Jacob, Neal L. BenowitzAbstract:The stable Isotope-Labeled Compound 3',-3'-dideuteronicotine (nicotine-d2) was used to investigate the disposition kinetics and effects of nicotine administered subcutaneously to 6 smokers. Plasma nicotine-d2 concentrations were measured for 8 h after subcutaneous injection of 4 doses (0.4, 0.8, 1.2, and 2.4 mg).
P. Jacob - One of the best experts on this subject based on the ideXlab platform.
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A clinical pharmacological study of subcutaneous nicotine
European Journal of Clinical Pharmacology, 1993Co-Authors: J. Le Houezec, P. Jacob, Neal L. BenowitzAbstract:The stable Isotope-Labeled Compound 3',-3'-dideuteronicotine (nicotine-d_2) was used to investigate the disposition kinetics and effects of nicotine administered subcutaneously to 6 smokers. Plasma nicotine-d_2 concentrations were measured for 8 h after subcutaneous injection of 4 doses (0.4, 0.8, 1.2, and 2.4 mg). Peak plasma nicotine concentration correlated well with the dose, averaging 2.8 to 14.8 ng/ml, 19 to 25 min after injection of the 0.4 mg and 2.4 mg doses, respectively. The plasma clearance over bioavailability ratio (CL/f) averaged 12 to 13 ml · min^−1 · kg^−1, similar to the clearance reported previously for intravenously administered nicotine. Thus, bioavailability appears to be approximately 100%. The heart rate response was more sensitive to the nicotine dose than the blood pressure response. Subjective effects showed large interindividual variability. The results reported herein may be useful in planning future studies. Administration of nicotine by the subcutaneous route appears to be a practical and safe method for studying the human pharmacology of nicotine.
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A clinical pharmacological study of subcutaneous nicotine
European journal of clinical pharmacology, 1993Co-Authors: J. Le Houezec, P. Jacob, Neal L. BenowitzAbstract:The stable Isotope-Labeled Compound 3',-3'-dideuteronicotine (nicotine-d2) was used to investigate the disposition kinetics and effects of nicotine administered subcutaneously to 6 smokers. Plasma nicotine-d2 concentrations were measured for 8 h after subcutaneous injection of 4 doses (0.4, 0.8, 1.2, and 2.4 mg).
Mutsuo Ishizaki - One of the best experts on this subject based on the ideXlab platform.
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Determination of Diphenylarsinic Acid in Plants and Biological Samples by HPLC/MS/MS Using a Stable Isotope Labeled Compound
BUNSEKI KAGAKU, 2006Co-Authors: Seiichi Ueno, Tatsumi Kitamura, Miki Nakamura, Keiko Ozone, Yasuyuki Shibata, Mutsuo IshizakiAbstract:A method for the determination of diphenylarsinic acid (DPAA) in plants and biological samples by high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS) using a stable Isotope Labeled Compound as an internal standard is described. After the sample was decomposed in 2 M sodium hydroxide by heating, an internal standard (DPAA-13C12) was added to the solution. The decomposed solution was shaked with a mixture of chloroform and n -hexane (1 : 4). After centrifugal separation, the organic layer was discarded. The aqueous layer was then adjusted to ca. 0.5 M hydrochloric acid solution, and cysteine and potassium iodide were added in order to extract DPAA efficiently in the chloroform. Extraction was carried out twice, and the chloroform layers were combined and evaporated. The extracts were dissolved in methanol or water in case of plants. When a colored solution was obtained, it was purified by an Oasis HLB solid-phase cartridge. In biological materials, the extracts were dissolved in a small volume of methanol, and then 0.5% nitric acid solution was added. When the mixture got cloudy, it was passed through a 0.20 μm of membranfilter. DPAA in the final solution was analyzed by HPLC/MS/MS. HPLC separation was performed with an ODS column using a linear gradient elution of an acetonitrile-water system containing 0.1% trifluoroacetic acid as the mobile phase. MS/MS was used in multiple reaction monitoring (MRM), employing electrospray ionization. The proposed method could determine DPAA in plants and biological samples with an average recovery of 99.4%. The coefficient of variation was as low as 6%. The calibration curve was linear between 0 and 30 ng/ml.
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determination of diphenylarsinic acid in plants and biological samples by hplc ms ms using a stable Isotope Labeled Compound
Bunseki Kagaku, 2006Co-Authors: Seiichi Ueno, Tatsumi Kitamura, Miki Nakamura, Keiko Ozone, Yasuyuki Shibata, Mutsuo IshizakiAbstract:A method for the determination of diphenylarsinic acid (DPAA) in plants and biological samples by high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS) using a stable Isotope Labeled Compound as an internal standard is described. After the sample was decomposed in 2 M sodium hydroxide by heating, an internal standard (DPAA-13C12) was added to the solution. The decomposed solution was shaked with a mixture of chloroform and n -hexane (1 : 4). After centrifugal separation, the organic layer was discarded. The aqueous layer was then adjusted to ca. 0.5 M hydrochloric acid solution, and cysteine and potassium iodide were added in order to extract DPAA efficiently in the chloroform. Extraction was carried out twice, and the chloroform layers were combined and evaporated. The extracts were dissolved in methanol or water in case of plants. When a colored solution was obtained, it was purified by an Oasis HLB solid-phase cartridge. In biological materials, the extracts were dissolved in a small volume of methanol, and then 0.5% nitric acid solution was added. When the mixture got cloudy, it was passed through a 0.20 μm of membranfilter. DPAA in the final solution was analyzed by HPLC/MS/MS. HPLC separation was performed with an ODS column using a linear gradient elution of an acetonitrile-water system containing 0.1% trifluoroacetic acid as the mobile phase. MS/MS was used in multiple reaction monitoring (MRM), employing electrospray ionization. The proposed method could determine DPAA in plants and biological samples with an average recovery of 99.4%. The coefficient of variation was as low as 6%. The calibration curve was linear between 0 and 30 ng/ml.
Roger N. Hayes - One of the best experts on this subject based on the ideXlab platform.
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High-resolution Isotope-dilution mass spectrometry using metabolism of Isotope-Labeled Compounds: application to drug metabolites.
Rapid communications in mass spectrometry : RCM, 2012Co-Authors: J. James Vrbanac, Allen Hilgers, Tyson Dubnicka, F. Barclay Shilliday, David Humphries, Roger N. HayesAbstract:RATIONALE Herein we describe a generic quantitative method using high-resolution, Isotope-dilution (HRID) metabolism of Isotope-Labeled Compounds and apply it to the analysis of drug metabolites (DMs) in human plasma. Metabolites (drug) in Safety Testing (MIST) application was one goal. METHODS Testosterone (T) and diclofenac (D) were chosen for mass defect characteristics. T, [14C]T, [13C3]T, D, [14C]D, and [13C6]D were metabolized separately in vitro to produce test metabolites. Liquid chromatography/radioactivity monitoring (LC/RAM) analysis was used to determine the concentration of the test metabolites in the incubates. The incubates containing 6β-hydroxy-T (6βHT), [13C3]6βHT, 4′-hydroxy-D (4′HD) and [13C6]4′HD were used to make standard curves. Plasma samples were prepared by 'dilute-and-shoot' and analyzed by LC/MS using SCIEX 5000 and Thermo Orbitrap instrumentation. RESULTS Human hepatic microsomes and the S9 fraction produced between 2–6 μM β-hydroxy-T and 4′-hydroxy-D at 60 min starting with 10 μM parent drug as determined by LC/RAM. It was assumed that the amounts of [13C3]6βHT and [13C6]4′HD produced were similar. Dilutions and standard curves were prepared in human plasma. Analysis of the DMs by LC/MS/MS and LC/HRMS exhibited linear responses over a useable range. CONCLUSIONS HRID with metabolism of an Isotope-Labeled Compound reduces the number of analytical variables considerably. Metabolism of the parent drug to DMs represents a simpler alternative quantitative method compared with traditional approaches. The method will have useful applications for evaluating MIST situations. Copyright © 2012 John Wiley & Sons, Ltd.