SENSITIVE AND RAPID ESTIMATION OF LAPATINIB, AN ANTICANCER DRUG IN SPIKED HUMAN PLASMA BY LC-MS/MS

  • Puran Singhal Kadi Sarva Vishwavidhyalaya
  • Priyanka A. Shah Gujarat University
  • Jaivik V. Shah Gujarat University
  • Mallika Sanyal St. Xavier’s College
  • Pranav S. Shrivastav Department of Chemistry, School of Sciences, Gujarat University, Navrangpura, Ahmedabad 380009, Gujarat, India

Abstract

Objective: The work presents a sensitive, selective and rapid determination of lapatinib, a potent anticancer drug in human plasma by liquid chromatography-tandem mass spectrometry.

Methods: Liquid-liquid extraction of lapatinib and lapatinib-d4, added as an internal standard (IS) was carried out from 100 µl plasma sample. Chromatographic analysis was performed on ACE C18 (100 mm × 4.6 mm, 5 µm) column using 10 mmol ammonium formate buffer (pH 3.5) and acetonitrile (10:90, v/v) as the mobile phase. The precursor ion → product ion transitions for lapatinib (m/z 581.1 → 365.2) and IS (m/z 585.1 → 365.0) were monitored on a triple quadrupole mass spectrometer in the positive electrospray ionization mode. The method was validated in accordance with the US FDA guidelines.

Results: A linear concentration range was established from 2.50-2500 ng/ml for lapatinib. The intra-batch and inter-batch precision were ≤ 4.81 %. The recovery of lapatinib and IS from plasma samples ranged from 88.7 to 95.8 % and 85.9 to 96.5 % respectively. The accuracy and precision (% CV) for the stability of lapatinib under different storage conditions showed a variation from 95.2 to 102.2 % and 1.19 to 4.35 % respectively at low and high QC levels. Under optimized chromatographic conditions, the retention time for lapatinib was 1.406 min with a total run time of 2.5 min for each sample.

Conclusion: The validation results demonstrate that the method is simple, accurate, precise and reproducible. The developed method can be readily used for pharmacokinetics/bioequivalence studies in patients as well as healthy subjects.

 

Keywords: Lapatinib, Lapatinib-d4, Liquid chromatography-tandem mass spectrometry, Human plasma, Sensitive, High-throughput

Downloads

Download data is not yet available.

References

1. Oakman C, Pestrin M, Zafarana E, Cantisani E, Di Leo A. Role of lapatinib in the first-line treatment of patients with metastatic breast cancer. Cancer Manage Res 2010;2:13-25.
2. Untch M, Luck HJ. Lapatinib-Member of a new generation of ErbB-targeting drugs. Breast Care 2010;5(Suppl):8-12.
3. Johnston S, Leary A. Lapatinib: a novel EGFR/HER2 tyrosine kinase inhibitor for cancer. Drugs Today 2006;42:441-53.
4. Van Erp NP, Gelderblom H, Guchelaar HJ. Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev 2009;35:692-706.
5. Koch KM, Reddy NJ, Cohen RB, Lewis NL, Whitehead B, Mackay K, et al. Effects of food on the relative bioavailability of lapatinib in cancer patients. J Clin Oncol 2009;8:1191-6.
6. Bence AK, Anderson EB, Halepota MA, Doukas MA, DeSimone PA, Davis GA, et al. Phase I pharmacokinetic studies evaluating single and multiple doses of oral GW572016, a dual EGFR-ErbB2 inhibitor, in healthy subjects. Invest New Drugs 2005;23:39-49.
7. Bai F, Freeman BB III, Fraga CH, Fouladi M, Stewart CF. Determination of lapatinib (GW572016) in human plasma by liquid chromatography-electrospray tandem mass spectrometry (LC–ESI-MS/MS). J Chromatogr B 2006;831:169-75.
8. Wu J, Wiegand R, LoRusso P, Li J. A stable isotope-labeled internal standard is essential for correcting for the interindividual variability in the recovery of lapatinib from cancer patient plasma in quantitative LC–MS/MS analysis. J Chromatogr B 2013;941:100-8.
9. Escudero-Ortiz V, Pérez-Ruixo JJ, Valenzuela B. Development and validation of a high-performance liquid chromatography-ultraviolet method for lapatinib quantification in human plasma. Ther Drug Monit 2013;35:796-802.
10. Musijowski J, Filist M, Rudzki PJ. Sensitive single quadrupole LC/MS method for determination of lapatinib in human plasma. Acta Poloniae Pharmaceutical-Drug Res 2014;71:1029-36.
11. Roche S, McMahon G, Clynes M, O'Connor R. Development of a high-performance liquid chromatographic–mass spectrometric method for the determination of cellular levels of the tyrosine kinase inhibitors lapatinib and dasatinib. J Chromatogr B 2009;877:3982-90.
12. Haouala A, Zanolari B, Rochat B, Montemurro M, Zaman K, Duchosal MA, et al. Therapeutic drug monitoring of the new targeted anticancer agents imatinib, nilotinib, dasatinib, sunitinib, sorafenib and lapatinib by LC tandem mass spectrometry. J Chromatogr B 2009;877:1982-96.
13. Bouchet S, Chauzit E, Ducint D, Castaing N, Canal-Raffin M, Moore N, et al. Simultaneous determination of nine tyrosine kinase inhibitors by 96-well solid-phase extraction and ultra-performance LC/MS-MS. Clin Chim Acta 2011;412:1060-7.
14. Micova K, Friedecky D, Faber E, Adam T. Isotope dilution direct injection mass spectrometry method for determination of four tyrosine kinase inhibitors in human plasma. Talanta 2012;93:307-13.
15. Götze L, Hegele A, Metzelder SK, Renz H, Nockher WA. Development and clinical application of a LC-MS/MS method for simultaneous determination of various tyrosine kinase inhibitors in human plasma. Clin Chim Acta 2012;413:143-9.
16. Lankheet NA, Hillebrand MJ, Rosing H, Schellens JH, Beijnen JH, Huitema AD. Method development and validation for the quantification of dasatinib, erlotinib, gefitinib, imatinib, lapatinib, nilotinib, sorafenib and sunitinib in human plasma by liquid chromatography coupled with tandem mass spectrometry. Biomed Chromatogr 2013;27:466-76.
17. Couchman L, Birch M, Ireland R, Corrigan A, Wickramasinghe S, Josephs D, et al. An automated method for the measurement of a range of tyrosine kinase inhibitors in human plasma or serum using turbulent flow liquid chromatography–tandem mass spectrometry. Anal Bioanal Chem 2012;403:1685-95.
18. Andriamanana I, Gana I, Duretz B, Hulin A. Simultaneous analysis of anticancer agents bortezomib, imatinib, nilotinib, dasatinib, erlotinib, lapatinib, sorafenib, sunitinib and vandetanib in human plasma using LC/MS/MS. J Chromatogr B 2013;926:83–91.
19. FDA, Guidance for Industry: Bioanalytical Method Validation. U. S. Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research (CDER), and Centre for Veterinary Medicine (CVM); 2001.
20. Shah PA, Sharma P, Shah JV, Sanyal M, Shrivastav PS. Simultaneous analysis of losartan, its active metabolite, and hydrochlorothiazide in human plasma by a UPLC-MS/MS method. Turk J Chem 2015;39:714-33.
21. Matuszewski BK. Standard line slopes as a measure of relative matrix effect in quantitative HPLC-MS bioanalysis. J Chromatogr B 2006;830:293-300.
Statistics
403 Views | 1661 Downloads
How to Cite
Singhal, P., P. A. Shah, J. V. Shah, M. Sanyal, and P. S. Shrivastav. “SENSITIVE AND RAPID ESTIMATION OF LAPATINIB, AN ANTICANCER DRUG IN SPIKED HUMAN PLASMA BY LC-MS/MS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 8, no. 1, Nov. 2015, pp. 214-20, https://innovareacademics.in/journals/index.php/ijpps/article/view/9532.
Section
Original Article(s)