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Simultaneous LC-MS/MS quantitation of acetaminophen and its glucuronide and sulfate metabolites from human dried blood spot samples collected by subjects

Li, Wenkui and Doherty, John and Kulmatycki, Kenneth and Smith, Harold and Tse, Francis (2012) Simultaneous LC-MS/MS quantitation of acetaminophen and its glucuronide and sulfate metabolites from human dried blood spot samples collected by subjects. Bioanalysis, 4 (12). pp. 1429-1443. ISSN 1757-6180

Abstract

Background: In support of a pilot clinical trial using acetaminophen as the model compound to assess DBS sampling as a suitable method for clinical pharmacokinetic (PK) studies, a novel sensitive LC-MS/MS method was developed and validated for the simultaneous determination of acetaminophen and its major metabolites, acetaminophen glucuronide and sulfate, in human DBS samples collected by subjects. Results: The validated assay dynamic range was from 50.0 to 5000 ng/mL for each compound using a 1/8 (3-mm) disc punched from a DBS. Baseline separation of the three analytes from each other was achieved to eliminate the possible impact on the analysis of the parent due to in-source conversion of the conjugated metabolites to the parent. The overall extraction efficiency was from 61.3 to 78.8 % for the three analytes by direct extraction using methanol. Conclusions: The validated assay method was successfully implemented in the pilot clinical study with the PK parameters in agreement with the values reported in literature

Item Type: Article
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Additional Information: Can archive pre-print (ie pre-refereeing)
Keywords: •Dried blood spot sampling: Technique in which blood is spotted on cellulose or polymer-based paper and dried. • Pharmacokinetics: Study of the movement of drugs in the body, including the processes of absorption, distribution and excretion. • Therapeutic drug monitoring. A branch of clinical chemistry and clinical pharmacology that specializes in the measurement of blood concentrations of drugs, especially those with a narrow therapeutic window, for improving patient care via dose adjustment of the drugs. • Remote PK sample collection: Collection of PK samples, normally DBS, conventionally carried out by patients themselves or their guardians after minimal training • DBS card. Cellulose or polymer based material of known characteristics, used for the collection, shipping and storage of dried blood spot samples.
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Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14
URI: https://oak.novartis.com/id/eprint/6887

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