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Verfasst von:Sauter, Max [VerfasserIn]   i
 Uhl, Philipp [VerfasserIn]   i
 Burhenne, Jürgen [VerfasserIn]   i
 Haefeli, Walter E. [VerfasserIn]   i
Titel:Application of triple quadrupole tandem mass spectrometry to the bioanalysis of collision-induced dissociation-resistant cyclic peptides
Titelzusatz:ultra-sensitive quantification of the somatostatin-analog pasireotide utilizing UHPLC-MS/MS
Verf.angabe:Max Sauter, Philipp Uhl, Jürgen Burhenne, Walter E. Haefeli
Jahr:2021
Fussnoten:Available online 5 November 2020 ; Gesehen am 19.02.2021
Titel Quelle:Enthalten in: Journal of pharmaceutical and biomedical analysis
Ort Quelle:New York, NY [u.a.] : Science Direct, 1983
Jahr Quelle:2021
Band/Heft Quelle:194(2021) Artikel-Nummer 113728, 7 Seiten
ISSN Quelle:1873-264X
Abstract:Cyclic peptides are considered collision-induced dissociation (CID)-resistant due to immobile protons, and the necessity of at least two consecutive dissociation reactions to produce fragments with deviating m/z values. Therefore, the bioanalysis of cyclic peptides by tandem mass spectrometry (MS/MS) poses a major challenge, especially on triple quadrupole (TQ) instruments. One of these peptides is the somatostatin analog pasireotide, a cyclic hexapeptide administered to treat Cushing’s disease and acromegaly. To support oral formulation development, sub-therapeutic quantification of pasireotide is highly beneficial. Regardless of the considered CID-resistance, we investigated the CID-characteristics of pasireotide and subsequently developed an ultra-sensitive UHPLC-MS/MS assay with a lower limit of quantification (LLOQ) of 5 pg/mL (4.9 pM) when using 100 μL of plasma and validated it according to the guidelines of the FDA and EMA. The achieved sensitivity, which is the highest thus far reported, demonstrates that TQ-MS/MS is a feasible approach to sensitive quantification of cyclic peptides despite their CID-resistance. Pasireotide was fast and efficiently extracted by protein depletion via precipitation using acetonitrile. Correlation coefficients > 0.99 were achieved for all calibration curves with linear regression. Inter-run and intra-run accuracy ranged from 89.4 to 99.3 % with corresponding precision of ≤ 7.5 % in the calibrated range, and from 94.6 to 105.6 % with corresponding precision of ≤ 14.5 % at the LLOQ. Quantification of 10-fold diluted samples showed an accuracy of 90.8 % and corresponding precision of 4.0 %. The assay was applied to the quantification of pasireotide plasma concentrations after intravenous administration to beagle dogs.
DOI:doi:10.1016/j.jpba.2020.113728
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext ; Verlag: https://doi.org/10.1016/j.jpba.2020.113728
 Volltext: https://www.sciencedirect.com/science/article/pii/S0731708520316149
 DOI: https://doi.org/10.1016/j.jpba.2020.113728
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:Collision-induced dissociation-resistant
 Cyclic peptide
 Pasireotide
 Plasma
 Tandem mass spectrometry
 UHPLC
K10plus-PPN:1748707159
Verknüpfungen:→ Zeitschrift

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