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Chromatography 2014, 1(2), 82-95; doi:10.3390/chromatography1020082
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

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Received: 26 March 2014; in revised form: 12 May 2014 / Accepted: 12 June 2014 / Published: 19 June 2014
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Abstract: 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.
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
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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.

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.

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.

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