A Novel UHPLC-MS/MS Method for the Quantification of Seven Opioids in Different Human Tissues.

Autor: Manca A; Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Corso Svizzera, 164, 10149 Turin, Italy., De Nicolò A; Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Corso Svizzera, 164, 10149 Turin, Italy., De Vivo ED; Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Corso Svizzera, 164, 10149 Turin, Italy., Ferrara M; Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy., Oh S; San Diego Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA 92037, USA., Khalili S; San Diego Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA 92037, USA., Higgins N; San Diego Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA 92037, USA., Deiss RG; San Diego Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA 92037, USA., Bonora S; Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, 10149 Turin, Italy., Cusato J; Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Corso Svizzera, 164, 10149 Turin, Italy., Palermiti A; Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Corso Svizzera, 164, 10149 Turin, Italy., Mula J; Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Corso Svizzera, 164, 10149 Turin, Italy.; CoQua Lab s.r.l., 10149 Turin, Italy., Gianella S; San Diego Division of Infectious Diseases and Global Public Health, University of California San Diego, La Jolla, CA 92037, USA., D'Avolio A; Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Corso Svizzera, 164, 10149 Turin, Italy.; CoQua Lab s.r.l., 10149 Turin, Italy.
Jazyk: angličtina
Zdroj: Pharmaceuticals (Basel, Switzerland) [Pharmaceuticals (Basel)] 2023 Jun 19; Vol. 16 (6). Date of Electronic Publication: 2023 Jun 19.
DOI: 10.3390/ph16060903
Abstrakt: Background: Opioids are considered the cornerstone of pain management: they show good efficacy as a first-line therapy for moderate to severe cancer pain. Since pharmacokinetic/pharmacodynamic information about the tissue-specific effect and toxicity of opioids is still scarce, their quantification in post-mortem autoptic specimens could give interesting insights.
Methods: We describe an ultra-high-performance liquid chromatography coupled with tandem mass spectrometry method for the simultaneous quantification of methadone, morphine, oxycodone, hydrocodone, oxymorphone, hydromorphone and fentanyl in several tissues: liver, brain, kidney, abdominal adipose tissue, lung and blood plasma. The presented method has been applied on 28 autoptic samples from different organs obtained from four deceased PLWH who used opioids for palliative care during terminal disease.
Results: Sample preparation was based on tissue weighing, disruption, sonication with drug extraction medium and a protein precipitation protocol. The extracts were then dried, reconstituted and injected onto the LX50 QSight 220 (Perkin Elmer, Milan, Italy) system. Separation was obtained by a 7 min gradient run at 40 °C with a Kinetex Biphenyl 2.6 µm, 2.1 × 100 mm. Concerning the analyzed samples, higher opioids concentrations were observed in tissues than in plasma. Particularly, O-MOR and O-COD showed higher concentrations in kidney and liver than other tissues (>15-20 times greater) and blood plasma (>100 times greater).
Conclusions: Results in terms of linearity, accuracy, precision, recovery and matrix effect fitted the recommendations of FDA and EMA guidelines, and the sensitivity was high enough to allow successful application on human autoptic specimens from an ethically approved clinical study, confirming its eligibility for post-mortem pharmacological/toxicological studies.
Databáze: MEDLINE
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