Login Register Cart 0
Generic placeholder image

Drug Metabolism Letters

Editor-in-Chief

ISSN (Print): 1872-3128
ISSN (Online): 1874-0758

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

The Effects of Special Patient Population Plasma on Pharmacokinetic Quantifications Using LC-MS/MS

Author(s): Dongmei Zhou*, Lifang Sun, Mai Nguyen, Li- Tain Yeh and David M. Wilson

Volume 13, Issue 2, 2019

Page: [111 - 122] Pages: 12

DOI: 10.2174/1872312813666191015162634

Abstract

Background: Clinical development of lesinurad, a selective uric acid reabsorption inhibitor, required analysis of lesinurad in plasma from special patient populations.

Methods: EMA and FDA bioanalytical method validation guidance have recommended studying matrix effects on quantitation if samples from special patient populations are to be analyzed. In addition to lesinurad (plasma protein binding 98.2%), the matrix effects from special population plasma on the quantitation of verapamil (PPB 89.6%), allopurinol and oxypurinol (PPB negligible) were also investigated.

Results: The plasma from special population patients had no matrix effects on the three quantification methods with stable isotope labeled internal standard, protein precipitation extraction, and LC-MS/MS detection. The validated lesinurad plasma quantification method was successfully applied for the pharmacokinetic evaluations to support the clinical studies in renal impaired patients.

Conclusion: Special population plasma did not affect quantitation of drugs with a wide range of plasma protein binding levels in human plasma. With the confirmation that there is no impact on quantification from the matrix, the bioanalytical method can be used to support the pharmacokinetic evaluations for clinical studies in special populations.

Keywords: Hepatic impairment, isobaric ions, LC-MS/MS, plasma protein binding, protein precipitation, renal impairment.

« Previous Next »
Graphical Abstract

[1]
Agency, E.M. Guidline on Bioanalytical Method ValidationS. M. H. European Medicines Agency, ed, 2012.
[2]
FDA. Bioanalytical Method Validation, 2001.
[3]
Yeh, L-T.; Shen, Z.; Kerr, B.; Hingorani, V.; Polvent, E.; Miner, J.N.; Zhou, D.; Nguyen, M.; Wilson, D.; Manhard, K.; Quart, B. RDEA594, A Novel Uricosuric Agent, Shows Impressive Reductions.Serum Urate Levels As Monotherapy And Substantial Additive Activity. In: Combination With Febuxostat In Normal Healthy Volunteers; Eular, 2010.
[4]
Perez-Ruiz, F.; Sundy, J.; Krishnan, E.; Hingorani, V.; Welp, J.; Rodgers, T.; Manhard, K.; Cravets, M.; Hagerty, D.; Quart, B. Efficacy and Safety of Lesinurad (RDEA594), a Novel URAT1 Inhibitor. Combination with Allopurinol in Allopurinol-Refractory Gout Patients: Results from a Randomized, Blinded, Placebo-Controlled, Phase 2B Extension Study; Eular, 2012.
[5]
Zhu, Y.; Pandya, B.J.; Choi, H.K. Prevalence of Gout and Hyperuricemia in the US General Population Arthritis & Rheumatism, 2011, 63(10), 3136-3141.
[6]
Zhu, Y.; Pandya, B.J.; Choi, H.K. Comorbidities of gout and hyperuricemia in the US general population: NHANES 2007-2008. Am. J. Med., 2012, 125(7), 679-687.e1.
[http://dx.doi.org/10.1016/j.amjmed.2011.09.033] [PMID: 22626509]
[7]
Pillinger, M.H.; Goldfarb, D.S.; Keenan, R.T. Gout and its comorbidities. Bull. NYU Hosp. Jt. Dis., 2010, 68(3), 199-203.
[PMID: 20969552]
[8]
Guidance for Indusry: Pharmacokinetics in Patients with Impaired Hepatic Functin: Study Design. Data Analysis, and Impact on Dosing and Labeling, 2003.
[9]
EMA. Note for Guidance on the Evaluation of the Pharmacokinetics of Medicinal Products in Patients with Impaired Renal Function, 2004.
[10]
EMA. Guideline on Bioanalytical Method Validation, 2012.
[11]
Kostiainen, R.; Kotiaho, T.; Kuuranne, T.; Auriola, S. Liquid chromatography/atmospheric pressure ionization-mass spectrometry in drug metabolism studies. J. Mass Spectrom., 2003, 38(4), 357-372.
[http://dx.doi.org/10.1002/jms.481] [PMID: 12717747]
[12]
Friedman, A.N.; Fadem, S.Z. Reassessment of Albumin as a Nutritional Marker in Kidney Disease. Journal of the american society of nephrology., 2010, 21(2), 223-230.
[http://dx.doi.org/10.1681/ASN.2009020213]
[13]
Patel, D. Matrix Effect in a View of LC-MS/MS: an Overview. Int. J. Pharma Bio Sci., 2011, 2(1), 559-564.
[14]
Chambers, E.; Wagrowski-Diehl, D.M.; Lu, Z.; Mazzeo, J.R. Systematic and comprehensive strategy for reducing matrix effects in LC/MS/MS analyses. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2007, 852(1-2), 22-34.
[http://dx.doi.org/10.1016/j.jchromb.2006.12.030] [PMID: 17236825]
[15]
Van Damme, T.; Lachová, M.; Lynen, F.; Szucs, R.; Sandra, P. Solid-phase extraction based on hydrophilic interaction liquid chromatography with acetone as eluent for eliminating matrix effects in the analysis of biological fluids by LC-MS. Anal. Bioanal. Chem., 2014, 406(2), 401-407.
[http://dx.doi.org/10.1007/s00216-013-7281-7] [PMID: 23978934]
[16]
EMA. Guideline on the Evaluation of the Pharmacokinetics of Medicinal Products in Patients with Impaired Hepatic Function, 2005.
[17]
Agrawal, M.; Swartz, R. Acute renal failure. Am. Fam. Physician, 2000, 61(7), 2077-2088.
[PMID: 10779250]
[18]
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 Analyt. Technol. Biomed. Life Sci., 2013, 941, 100-108.
[http://dx.doi.org/10.1016/j.jchromb.2013.10.011] [PMID: 24189203]
[19]
Wang, S.; Cyronak, M.; Yang, E. Does a stable isotopically labeled internal standard always correct analyte response? A matrix effect study on a LC/MS/MS method for the determination of carvedilol enantiomers in human plasma. J. Pharm. Biomed. Anal., 2007, 43(2), 701-707.
[http://dx.doi.org/10.1016/j.jpba.2006.08.010] [PMID: 16959461]
[20]
Jemal, M.; Schuster, A.; Whigan, D.B. Liquid chromatography/tandem mass spectrometry methods for quantitation of mevalonic acid in human plasma and urine: method validation, demonstration of using a surrogate analyte, and demonstration of unacceptable matrix effect in spite of use of a stable isotope analog internal standard. Rapid Commun. Mass Spectrom., 2003, 17(15), 1723-1734.
[http://dx.doi.org/10.1002/rcm.1112] [PMID: 12872277]
[21]
Keefe, D.L.; Yee, Y-G.; Kates, R.E. Verapamil Protein Binding in Patients and in Normal Subjects. Clinical Pharmacology & Therapeutics., 1981, 12(29(1)), 21-26.
[http://dx.doi.org/10.1038/clpt.1981.4]
[22]
Turnheim, K.; Krivanek, P.; Oberbauer, R. Pharmacokinetics and pharmacodynamics of allopurinol in elderly and young subjects. Br. J. Clin. Pharmacol., 1999, 48(4), 501-509.
[http://dx.doi.org/10.1046/j.1365-2125.1999.00041.x] [PMID: 10583019]
[23]
Ghosh, C.; Shinde, C.P.; Chakraborty, B.S. Ionization Polarity as a Cause of Matrix Effects, its Removal and Estimation in ESI-LC-MS/MS Bio-analysis. Journal of Analytical & Bioanalytical Techniquesh., 2010, 1(2), 1-6.
[http://dx.doi.org/10.4172/2155-9872.1000106]
[24]
King, R.; Bonfiglio, R.; Fernandez-Metzler, C.; Miller-Stein, C.; Olah, T. Mechanistic investigation of ionization suppression in electrospray ionization. J. Am. Soc. Mass Spectrom., 2000, 11(11), 942-950.
[http://dx.doi.org/10.1016/S1044-0305(00)00163-X] [PMID: 11073257]
[25]
Gillen, M.; Valdez, S.; Zhou, D.; Kerr, B.; Caroline, A. Lee, and Z. Shen, “Effects of renal function on pharmacokinetics and pharmacodynamics of lesinurad in adult volunteers. Drug Des. Devel. Ther., 2016, 10, 8.
[http://dx.doi.org/10.2147/DDDT.S119944]
[26]
Marchi, I.; Rudaz, S.; Selman, M.; Veuthey, J-L. Evaluation of the influence of protein precipitation prior to on-line SPE-LC-API/MS procedures using multivariate data analysis. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2007, 845(2), 244-252.
[http://dx.doi.org/10.1016/j.jchromb.2006.08.045] [PMID: 17030156]

Rights & Permissions Print Cite
Article Metrics
21
9
© 2024 Bentham Science Publishers | Privacy Policy