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
Abstract
:1. Introduction
2. Experimental Section
2.1. Materials
2.2. Preparation of Stock Solutions
2.3. Sample Preparation
2.4. Instrument Conditions
2.5. Validation
2.5.1. Linearity
2.5.2. Accuracy and Precision
2.5.3. Stability
2.5.4. Extraction Recovery and Matrix Effects
2.6. Clinical Application
3. Results and Discussion
3.1. Selectivity
3.2. Linearity, Accuracy and Precision
Nominal (ng/mL) | GM (ng/mL) | SD (ng/mL) | DEV (%) | CV (%) | n |
---|---|---|---|---|---|
0.50 | 0.52 | 0.06 | 3.00 | 11.88 | 8 |
5.0 | 5.38 | 0.31 | 7.50 | 5.78 | 8 |
25 | 24.99 | 1.17 | −0.04 | 4.67 | 8 |
100 | 104.30 | 2.58 | 4.30 | 2.47 | 8 |
500 | 494.13 | 16.09 | −1.17 | 3.26 | 8 |
1000 | 1001.39 | 36.39 | 0.14 | 3.63 | 8 |
2000 | 1963.61 | 74.09 | −1.82 | 3.77 | 8 |
5000 | 4594.08 | 94.75 | −8.12 | 2.06 | 8 |
Nominal (ng/mL) | GM (ng/mL) | SD (ng/mL) | DEV (%) | WRP (%) | BRP (%) | n |
---|---|---|---|---|---|---|
0.5 (LLOQ) | 0.49 | 0.05 | −2.60 | 9.10 | 1.75 | 20 |
1.0 (LQC) | 1.01 | 0.12 | 1.10 | 10.79 | 3.65 | 20 |
900 (MQC) | 876.89 | 39.72 | −2.57 | 1.53 | 2.77 | 20 |
4500 (HQC) | 4105.04 | 133.88 | −8.78 | 1.59 | 1.85 | 20 |
50,000 (DQC) | 48,028.85 | 1397.15 | −3.94 | 2.20 | 1.24 | 20 |
3.3. Stability
6.50 ng/mL (low) | 150 ng/mL (mid) | 1600 (high) | ||||
---|---|---|---|---|---|---|
Freeze/Thaw Cycles | GM (ng/mL) | DEV from Fresh (%) | GM (ng/mL) | DEV from Fresh (%) | GM (ng/mL) | DEV from Fresh (%) |
0 (Fresh) | 5.94 | - | 149.52 | - | 1489.40 | - |
1 | 6.10 | 2.69 | 146.70 | −1.89 | 1512.20 | 1.53 |
2 | 6.22 | 4.71 | 156.40 | 4.60 | 1606.48 | 7.86 |
3 | 6.50 | 9.43 | 153.66 | 2.77 | 1572.46 | 5.58 |
3.4. Extraction Recovery and Matrix Effects
3.5. Clinical Application
4. Conclusions
Acknowledgments
Authors Contributions
Disclaimer
Conflicts of Interest
References
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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
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 StyleRoth, Jeffrey, Cody J. Peer, Baskar Mannargudi, Helen Swaisland, Jung-Min Lee, Elise C. Kohn, and William D. Figg. 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
APA StyleRoth, J., Peer, C. J., Mannargudi, B., Swaisland, H., Lee, J.-M., Kohn, E. C., & Figg, W. 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(2), 82-95. https://doi.org/10.3390/chromatography1020082