Determination of naloxegol in human biological matrices

Naloxegol is an oral peripherally acting μ-opioid receptor antagonist approved for the treatment of opioid-induced constipation. Sensitive, robust, bioanalytical methods were required to quantitate naloxegol in human biological matrices as part of the clinical development program. Analytical plasma...

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Published inBioanalysis Vol. 9; no. 8; pp. 609 - 619
Main Authors Li, Yan, Hoffmann, Mark, Severin, Paul
Format Journal Article
LanguageEnglish
Published England Future Science Ltd 01.04.2017
Subjects
Analgesics, Opioid - adverse effects
Chromatography, Liquid - methods
clinical
Constipation - chemically induced
Constipation - drug therapy
Humans
LC-MS
Limit of Detection
Morphinans - blood
Morphinans - urine
naloxegol
Narcotic Antagonists - blood
Narcotic Antagonists - urine
Polyethylene Glycols
Receptors, Opioid, mu - antagonists & inhibitors
Solid Phase Extraction - methods
Tandem Mass Spectrometry - methods
clinical
naloxegol
LC–MS
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Abstract Naloxegol is an oral peripherally acting μ-opioid receptor antagonist approved for the treatment of opioid-induced constipation. Sensitive, robust, bioanalytical methods were required to quantitate naloxegol in human biological matrices as part of the clinical development program. Analytical plasma samples were prepared using Solid Phase Extraction (SPE) coupled with concentration. The method's linearity was established at 0.1-50 ng/ml with up to 100-fold dilution. Urine samples were analyzed directly postdilution; dialysate samples were extracted by supported liquid extraction. Sensitive liquid chromatography/mass spectrometry (LC-MS/MS) assays were developed and validated, and demonstrated acceptable precision, accuracy and selectivity for naloxegol in the appropriate matrices. Methods for quantifying naloxegol in human biological matrices have been successfully validated.
AbstractList Naloxegol is an oral peripherally acting μ-opioid receptor antagonist approved for the treatment of opioid-induced constipation. Sensitive, robust, bioanalytical methods were required to quantitate naloxegol in human biological matrices as part of the clinical development program. Analytical plasma samples were prepared using Solid Phase Extraction (SPE) coupled with concentration. The method's linearity was established at 0.1-50 ng/ml with up to 100-fold dilution. Urine samples were analyzed directly postdilution; dialysate samples were extracted by supported liquid extraction. Sensitive liquid chromatography/mass spectrometry (LC-MS/MS) assays were developed and validated, and demonstrated acceptable precision, accuracy and selectivity for naloxegol in the appropriate matrices. Methods for quantifying naloxegol in human biological matrices have been successfully validated.
Author Hoffmann, Mark
Li, Yan
Severin, Paul
AuthorAffiliation 2Covance Laboratories, Inc., 3301 Kinsman Blvd, Madison, WI 53704, USA
1Clinical Sample Science, Early Clinical Development, AstraZeneca, 35 Gatehouse Drive, Waltham, MA 02451, USA
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SubjectTerms Analgesics, Opioid - adverse effects
Chromatography, Liquid - methods
clinical
Constipation - chemically induced
Constipation - drug therapy
Humans
LC-MS
Limit of Detection
Morphinans - blood
Morphinans - urine
naloxegol
Narcotic Antagonists - blood
Narcotic Antagonists - urine
Polyethylene Glycols
Receptors, Opioid, mu - antagonists & inhibitors
Solid Phase Extraction - methods
Tandem Mass Spectrometry - methods
Title Determination of naloxegol in human biological matrices
URI http://dx.doi.org/10.4155/bio-2016-0253
https://www.ncbi.nlm.nih.gov/pubmed/28504549
Volume 9
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