LC–MS/MS assay for the quantitation of the ribonucleotide reductase inhibitor triapine in human plasma

Julia Matsumoto, Brian F. Kiesel, Robert A. Parise, Jianxia Guo, Sarah Taylor, Marilyn Huang, Julie L. Eiseman, S. Percy Ivy, Charles Kunos, Edward Chu, Jan H. Beumer

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The ribonucleotide reductase inhibitor and radiosensitizer triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP), NSC 663249) is clinically being evaluated via the intravenous (IV) route for the treatment of cervical and vulvar cancer in combination with primary cisplatin chemoradiation. The need for a 2-h infusion and frequent administration of triapine is logistically challenging, prompting us to pursue oral (PO) administration. In support of the clinical trial investigating oral triapine in combination with chemoradiation, we developed and validated a novel LC–MS/MS assay for the quantification of triapine in 50 μL human plasma. After protein precipitation, chromatographic separation of the supernatant was achieved with a Shodex ODP2 column and an isocratic acetonitrile-water mobile phase with 10% ammonium acetate. Detection with an ABI 4000 mass spectrometer utilized electrospray positive mode ionization. The assay was linear from 3 to 3,000 ng/mL and proved to be accurate (97.1–103.1%) and precise (<7.4% CV), and met the U.S. FDA guidance for bioanalytical method validation. This LC–MS/MS assay will be an essential tool to further define the pharmacokinetics and oral bioavailability of triapine.

Original languageEnglish (US)
Pages (from-to)154-160
Number of pages7
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume146
DOIs
StatePublished - Nov 30 2017
Externally publishedYes

Fingerprint

Plasma (human)
Ribonucleotide Reductases
Assays
Pharmacokinetics
Vulvar Neoplasms
Mass spectrometers
Cisplatin
Ionization
3-aminopyridine-2-carboxaldehyde thiosemicarbazone
Uterine Cervical Neoplasms
Biological Availability
Oral Administration
Clinical Trials
Water
Proteins

Keywords

  • Assay
  • Tandem mass spectrometry
  • Triapine
  • Validation

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

Cite this

LC–MS/MS assay for the quantitation of the ribonucleotide reductase inhibitor triapine in human plasma. / Matsumoto, Julia; Kiesel, Brian F.; Parise, Robert A.; Guo, Jianxia; Taylor, Sarah; Huang, Marilyn; Eiseman, Julie L.; Ivy, S. Percy; Kunos, Charles; Chu, Edward; Beumer, Jan H.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 146, 30.11.2017, p. 154-160.

Research output: Contribution to journalArticle

Matsumoto, J, Kiesel, BF, Parise, RA, Guo, J, Taylor, S, Huang, M, Eiseman, JL, Ivy, SP, Kunos, C, Chu, E & Beumer, JH 2017, 'LC–MS/MS assay for the quantitation of the ribonucleotide reductase inhibitor triapine in human plasma', Journal of Pharmaceutical and Biomedical Analysis, vol. 146, pp. 154-160. https://doi.org/10.1016/j.jpba.2017.08.036
Matsumoto, Julia ; Kiesel, Brian F. ; Parise, Robert A. ; Guo, Jianxia ; Taylor, Sarah ; Huang, Marilyn ; Eiseman, Julie L. ; Ivy, S. Percy ; Kunos, Charles ; Chu, Edward ; Beumer, Jan H. / LC–MS/MS assay for the quantitation of the ribonucleotide reductase inhibitor triapine in human plasma. In: Journal of Pharmaceutical and Biomedical Analysis. 2017 ; Vol. 146. pp. 154-160.
@article{618cc7f106a3437ba5e453883ddfb2e5,
title = "LC–MS/MS assay for the quantitation of the ribonucleotide reductase inhibitor triapine in human plasma",
abstract = "The ribonucleotide reductase inhibitor and radiosensitizer triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP), NSC 663249) is clinically being evaluated via the intravenous (IV) route for the treatment of cervical and vulvar cancer in combination with primary cisplatin chemoradiation. The need for a 2-h infusion and frequent administration of triapine is logistically challenging, prompting us to pursue oral (PO) administration. In support of the clinical trial investigating oral triapine in combination with chemoradiation, we developed and validated a novel LC–MS/MS assay for the quantification of triapine in 50 μL human plasma. After protein precipitation, chromatographic separation of the supernatant was achieved with a Shodex ODP2 column and an isocratic acetonitrile-water mobile phase with 10{\%} ammonium acetate. Detection with an ABI 4000 mass spectrometer utilized electrospray positive mode ionization. The assay was linear from 3 to 3,000 ng/mL and proved to be accurate (97.1–103.1{\%}) and precise (<7.4{\%} CV), and met the U.S. FDA guidance for bioanalytical method validation. This LC–MS/MS assay will be an essential tool to further define the pharmacokinetics and oral bioavailability of triapine.",
keywords = "Assay, Tandem mass spectrometry, Triapine, Validation",
author = "Julia Matsumoto and Kiesel, {Brian F.} and Parise, {Robert A.} and Jianxia Guo and Sarah Taylor and Marilyn Huang and Eiseman, {Julie L.} and Ivy, {S. Percy} and Charles Kunos and Edward Chu and Beumer, {Jan H.}",
year = "2017",
month = "11",
day = "30",
doi = "10.1016/j.jpba.2017.08.036",
language = "English (US)",
volume = "146",
pages = "154--160",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
issn = "0731-7085",
publisher = "Elsevier",

}

TY - JOUR

T1 - LC–MS/MS assay for the quantitation of the ribonucleotide reductase inhibitor triapine in human plasma

AU - Matsumoto, Julia

AU - Kiesel, Brian F.

AU - Parise, Robert A.

AU - Guo, Jianxia

AU - Taylor, Sarah

AU - Huang, Marilyn

AU - Eiseman, Julie L.

AU - Ivy, S. Percy

AU - Kunos, Charles

AU - Chu, Edward

AU - Beumer, Jan H.

PY - 2017/11/30

Y1 - 2017/11/30

N2 - The ribonucleotide reductase inhibitor and radiosensitizer triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP), NSC 663249) is clinically being evaluated via the intravenous (IV) route for the treatment of cervical and vulvar cancer in combination with primary cisplatin chemoradiation. The need for a 2-h infusion and frequent administration of triapine is logistically challenging, prompting us to pursue oral (PO) administration. In support of the clinical trial investigating oral triapine in combination with chemoradiation, we developed and validated a novel LC–MS/MS assay for the quantification of triapine in 50 μL human plasma. After protein precipitation, chromatographic separation of the supernatant was achieved with a Shodex ODP2 column and an isocratic acetonitrile-water mobile phase with 10% ammonium acetate. Detection with an ABI 4000 mass spectrometer utilized electrospray positive mode ionization. The assay was linear from 3 to 3,000 ng/mL and proved to be accurate (97.1–103.1%) and precise (<7.4% CV), and met the U.S. FDA guidance for bioanalytical method validation. This LC–MS/MS assay will be an essential tool to further define the pharmacokinetics and oral bioavailability of triapine.

AB - The ribonucleotide reductase inhibitor and radiosensitizer triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP), NSC 663249) is clinically being evaluated via the intravenous (IV) route for the treatment of cervical and vulvar cancer in combination with primary cisplatin chemoradiation. The need for a 2-h infusion and frequent administration of triapine is logistically challenging, prompting us to pursue oral (PO) administration. In support of the clinical trial investigating oral triapine in combination with chemoradiation, we developed and validated a novel LC–MS/MS assay for the quantification of triapine in 50 μL human plasma. After protein precipitation, chromatographic separation of the supernatant was achieved with a Shodex ODP2 column and an isocratic acetonitrile-water mobile phase with 10% ammonium acetate. Detection with an ABI 4000 mass spectrometer utilized electrospray positive mode ionization. The assay was linear from 3 to 3,000 ng/mL and proved to be accurate (97.1–103.1%) and precise (<7.4% CV), and met the U.S. FDA guidance for bioanalytical method validation. This LC–MS/MS assay will be an essential tool to further define the pharmacokinetics and oral bioavailability of triapine.

KW - Assay

KW - Tandem mass spectrometry

KW - Triapine

KW - Validation

UR - http://www.scopus.com/inward/record.url?scp=85028696779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028696779&partnerID=8YFLogxK

U2 - 10.1016/j.jpba.2017.08.036

DO - 10.1016/j.jpba.2017.08.036

M3 - Article

C2 - 28881312

AN - SCOPUS:85028696779

VL - 146

SP - 154

EP - 160

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

ER -