In order to find a correlation between Fentanyl action on pain and inter-individual variability in different cancer patients, the pharmacokinetic characterization of the drug becomes essential. Therefore, a gas chromatographic-mass spectrometric (GC-MS) in SIM mode analytical procedure has been developed and validated for the determination of Fentanyl in human blood. The sample preparation consisted of a liquid-liquid extraction (LLE) from whole blood. The analysis were carried out with Agilent 7820 A series gas chromatograph equipped with a 5977E series mass selective single quadrupole detector (MSD) with an electron impact (EI) source (70 eV), under a temperature gradient elution. The limit of detection (LoD) and the limit of quantification (LoQ) values were found to be 5.60E-02 +/- 3.50E-02 ng mL(-1) and 1.86E-01 +/- 1.18E-01 ng mL(-1) respectively. The developed method was found selective and sensitive and therefore suitable for a fast determination of Fentanyl in human blood and for its pharmacokinetic characterization. Blood samples from 31 cancer patients treated with transdermal Fentanyl (doses in the range of 12-100 mu g h(-1)) were collected at fixed intervals during an overall exposure time of 72 h. The analysis of data and the pharmacokinetic parameters revealed dissimilar pharmacokinetic profiles in the patients examined. Patients were therefore grouped in three categories representing the different trends observed: high, medium and slow responders. These preliminary data provided significant outcomes for a correlation to clinical response.

Fentanyl pharmacokinetics in blood of cancer patients by Gas Chromatography - Mass Spectrometry

Montanari, Serena;De Simone, Angela
;
2022-01-01

Abstract

In order to find a correlation between Fentanyl action on pain and inter-individual variability in different cancer patients, the pharmacokinetic characterization of the drug becomes essential. Therefore, a gas chromatographic-mass spectrometric (GC-MS) in SIM mode analytical procedure has been developed and validated for the determination of Fentanyl in human blood. The sample preparation consisted of a liquid-liquid extraction (LLE) from whole blood. The analysis were carried out with Agilent 7820 A series gas chromatograph equipped with a 5977E series mass selective single quadrupole detector (MSD) with an electron impact (EI) source (70 eV), under a temperature gradient elution. The limit of detection (LoD) and the limit of quantification (LoQ) values were found to be 5.60E-02 +/- 3.50E-02 ng mL(-1) and 1.86E-01 +/- 1.18E-01 ng mL(-1) respectively. The developed method was found selective and sensitive and therefore suitable for a fast determination of Fentanyl in human blood and for its pharmacokinetic characterization. Blood samples from 31 cancer patients treated with transdermal Fentanyl (doses in the range of 12-100 mu g h(-1)) were collected at fixed intervals during an overall exposure time of 72 h. The analysis of data and the pharmacokinetic parameters revealed dissimilar pharmacokinetic profiles in the patients examined. Patients were therefore grouped in three categories representing the different trends observed: high, medium and slow responders. These preliminary data provided significant outcomes for a correlation to clinical response.
2022
219
114913
114921
Cancer patients; Clinical monitoring; Fentanyl; Gas chromatography-mass spectrometry; Liquid-liquid extraction; Whole blood pharmacokinetics; Gas Chromatography-Mass Spectrometry; Humans; Limit of Detection; Liquid-Liquid Extraction; Fentanyl; Neoplasms
Montanari, Serena; Davani, Lara; Terenzi, Cristina; Maltoni, Marco; Andrisano, Vincenza; De Simone, Angela; Ricci, Marianna
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1878285
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