Next Article in Journal
Cu Purification Using an Extraction Resin for Determination of Isotope Ratios by Multicollector ICP-MS
Previous Article in Journal
An Isocratic Toxic Chemical-Free Mobile Phase HPLC-PDA Analysis of Malachite Green and Leuco-Malachite Green
Please note that, as of 1 January 2016, Chromatography has been renamed to Separations and is now published here.
Article

A Sensitive and Robust Ultra HPLC Assay with Tandem Mass Spectrometric Detection for the Quantitation of the PARP Inhibitor Olaparib (AZD2281) in Human Plasma for Pharmacokinetic Application

1
Clinical Pharmacology Program, Office of the Clinical Director, National Cancer Institute, Bethesda, MD 20892, USA
2
AstraZeneca Pharmaceuticals, Alderley Park Macclesfield, Cheshire SK10 4TG, UK
3
Medical Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA
*
Author to whom correspondence should be addressed.
Chromatography 2014, 1(2), 82-95; https://doi.org/10.3390/chromatography1020082
Received: 26 March 2014 / Revised: 12 May 2014 / Accepted: 12 June 2014 / Published: 19 June 2014
Olaparib (AZD2281) is an orally active PARP-1 inhibitor, primarily effective against cancers with BRCA1/2 mutations. It is currently in Phase III development and has previously been investigated in numerous clinical trials, both as a single agent and in combination with chemotherapy. Despite this widespread testing, there is only one published method that provides assay details and stability studies for olaparib alone. A more sensitive uHPLC-MS/MS method for the quantification of olaparib in human plasma was developed, increasing the range of quantification at both ends (0.5–50,000 ng/mL) compared to previously published methods (10–5,000 ng/mL). The wider range encompasses CMAX levels produced by typical olaparib doses and permits better pharmacokinetic modeling of olaparib elimination. This assay also utilizes a shorter analytical runtime, allowing for more rapid quantification and reduced use of reagents. A liquid-liquid extraction was followed by chromatographic separation on a Waters UPLC® BEH C18 column (2.1 × 50 mm, 1.7 µm) and mass spectrometric detection. The mass transitions m/z 435.4→281.1 and m/z 443.2→281.1 were used for olaparib and the internal standard [2H8]-olaparib, respectively. The assay proved to be accurate (<9% deviation) and precise (CV < 11%). Stability studies showed that olaparib is stable at room temperature for 24 h. in whole blood, at 4 °C for 24 h post-extraction, at −80 °C in plasma for at least 19 months, and through three freeze-thaw cycles. This method proved to be robust for measuring olaparib levels in clinical samples from a Phase I trial. View Full-Text
Keywords: poly(ADP-ribose) polymerase inhibitor; olaparib; ultra-high performance liquid chromatography; tandem mass spectrometry; pharmacokinetics poly(ADP-ribose) polymerase inhibitor; olaparib; ultra-high performance liquid chromatography; tandem mass spectrometry; pharmacokinetics
Show Figures

Figure 1

MDPI and ACS Style

Roth, J.; Peer, C.J.; Mannargudi, B.; Swaisland, H.; Lee, J.-M.; Kohn, E.C.; Figg, W.D. A Sensitive and Robust Ultra HPLC Assay with Tandem Mass Spectrometric Detection for the Quantitation of the PARP Inhibitor Olaparib (AZD2281) in Human Plasma for Pharmacokinetic Application. Chromatography 2014, 1, 82-95. https://doi.org/10.3390/chromatography1020082

AMA Style

Roth J, Peer CJ, Mannargudi B, Swaisland H, Lee J-M, Kohn EC, Figg WD. A Sensitive and Robust Ultra HPLC Assay with Tandem Mass Spectrometric Detection for the Quantitation of the PARP Inhibitor Olaparib (AZD2281) in Human Plasma for Pharmacokinetic Application. Chromatography. 2014; 1(2):82-95. https://doi.org/10.3390/chromatography1020082

Chicago/Turabian Style

Roth, Jeffrey; Peer, Cody J.; Mannargudi, Baskar; Swaisland, Helen; Lee, Jung-Min; Kohn, Elise C.; Figg, William D. 2014. "A Sensitive and Robust Ultra HPLC Assay with Tandem Mass Spectrometric Detection for the Quantitation of the PARP Inhibitor Olaparib (AZD2281) in Human Plasma for Pharmacokinetic Application" Chromatography 1, no. 2: 82-95. https://doi.org/10.3390/chromatography1020082

Find Other Styles

Article Access Map by Country/Region

1
Only visits after 24 November 2015 are recorded.
Back to TopTop