QUANTITATIVE DETERMINATION OF CRIZOTINIB IN HUMAN PLASMA WITH HIGHPERFORMANCE LIQUID CHROMATOGRAPHY AND ULTRAVIOLET DETECTION
Objective: A rapid, sensitive, selective, and reproducible reversed-phase high-performance liquid chromatographic method has been developed and validated for the determination of crizotinib (CRZ), a tyrosine kinase inhibitor for targeted therapy of anaplastic lymphoma kinase-positive non-small-cell lung cancer.
Methods: The chromatographic separation was carried out in an isocratic mode on an YMC ODS C18 column with a mobile phase consisting of methanol and water containing 0.1% orthophosphoric acid in the ratio of 50:50 v/v at a flow rate of 0.6 ml/min. The run time was maintained for 10 min and detection was monitored at 267 nm. The method involved reproducible liquid-liquid extraction of drug from human plasma using diethyl ether as extracting solvent.
Results: CRZ and internal standard retention times were 6.86 and 7.94 min, respectively. Calibration curves were linear over a concentration range of 20.41–2041.14 ng/ml with correlation coefficient 0.9994. The lower limit of quantification for CRZ in plasma was 20 ng/ml. No endogenous substances were found to interfere with the peaks of drug and internal standard. The intra- and inter-day precision was <9.0% and the accuracy ranged from 97% to 112% over the linear range. All stability studies showed that CRZ in plasma sample was stable.
Conclusion: This method was found to be simple, selective, precise, accurate, and cost-effective. Hence, the method can be successfully applied to analyze the CRZ concentration in plasma samples for pharmacokinetic and bioequivalence studies.
2. Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, et al. First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Eng J Med 2014;371:2167-77.
3. Shaw AT, Kim DW, Nakagawa K, Seto T, Crinó L, Ahn MJ, et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 2013;368:2385-94.
4. Li C, Alvey C, Bello A, Wilner KD, Tan W. Pharmacokinetics of crizotinib (PF-02341066) in patients with advanced non-small cell lung cancer (NSCLC) and other solid tumors. J Clin Oncol 2011;29:13065.
5. Herbrink M, de Vries N, Rosing H, Huitema AD, Nuijen B, Schellens JH, et al. Development and validation of a liquid chromatography-tandem mass spectrometry analytical method for the therapeutic drug monitoring of eight novel anticancer drugs. Biomed Chromatogr 2018;32:1-9.
6. Sparidans RW, Tang SC, Nguyen LN, Schinkel AH, Schellens JH, Beijnen JH. Liquid chromatography-tandem mass spectrometric assay for the ALK inhibitor crizotinib in mouse plasma. J Chromatogr B 2012;905:150-4.
7. Wani T, Lqbal M, Darwish I, Khalil N, Zargar S. Development and validation of sensitive UPLC-MS/MS based method for the estimation of crizotinib in human plasma. Dig J Nanometer Biostruct 2014;9:693 704.
8. Huang X, Cai J, Wang X. LC-MS determination of crizotinib in rat plasma and it application to a pharmacokinetic study. Lat Am J Pharm 2014;33:1188-92.
9. Michael SR, David CT, Alberto B, Clinton FS. Determination of crizotinib in human and mouse plasma by liquid chromatography electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). J Chromatogr B 2014;960:151-7.
10. Khalil NY, Wani TA, Darwish IA, Al-Majed RA. Highly sensitive HPLC method with non-extractive sample preparation and fluorescence detection for determination of crizotinib in human plasma. Lat Am J Pharm 2014;33:1019-26.
11. Hany WD, Ahmed HB, Ibrahim AD. Enhanced spectrofluorimetric determination of the multitargeted tyrosinase kinase inhibitor crizotinib in human plasma via micelle-mediated approach. Trop J Pharm Res 2016;15:2209-17.
12. Vijayakumar B, Suman E, Sreekanth G. Estimation of crizotinib in capsule dosage form by RP-HPLC. IOSR J Pharm Biol Sci 2016;11:93 103.
13. Guidance for Industry. Bioanalytical Method Validation. Rockville, MD: U.S. Department of Health and Human Services, Food and Drug Administration Center for Drug Evaluation and Research; 2001.
14. Singh Y, Hidau MK, Misra A, Kushwaha HN, Tiwari A, Sharma AK, et al. UFLC method development and validation of a novel triethylamine containing thiophene S006-830-an antitubercular molecule and its application to pharmacokinetic and bioavailability studies in SD rats. Drug Test Anal 2015;7:721-6.
15. Togami K, Fukuda K, Yamaguchi K, Chono S, Tada H. Facile and sensitive HPLC-UV method for determination of nintedanib in rat plasma. Int J Pharm Pharm Sci 2018;10:133-7.
16. Kraak JC, Crombeen JP, Brelmer DD, Spewer P. Sample Pretreatment in Bio-Analysis. Amsterdam: Elsevier; 1987. p. 123-35.
17. Madhavi S, Rani AP. Bioanalytical method development and valiation for the determination of sofosbuvir from human plasma. Int J Pharm Pharm Sci 2017;9:35-41.
18. Jinesh BN, Bannimath G. Simultaneous estimation of clopidogrel and atorvastatin in human plasma using bio-analytical RP-Ultra fast liquid chromatographic method. Int J Curr Pharm Res 2015;7:30-5.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.