Z. Pan, H. Scheerens, S. J. Li, B. Schultz, P. A. Sprengeler et al.,

K. C. Sweeney, P. G. Scott, D. A. Grothaus, J. M. Jeffery, L. A. Spoerke et al., , vol.366

J. T. Dalrymple and . Palmer, Discovery of selective irreversible inhibitors for Bruton's tyrosine kinase, p.367

, Chem. Med. Chem, vol.2, pp.58-61, 2007.

, Patient Resources & Information for IMBRUVICA®, p.7, 2018.

, Development history and FDA approval process for Imbruvica

, Imbruvica -Authorisation details

M. Dreyling, W. Jurczak, M. Jerkeman, R. S. Silva, C. Rusconi et al.,

M. Joao, G. Witzens-harig, I. Hess, S. G. Bence-bruckler, J. Cho et al.,

S. Traina, N. Balasubramanian, S. Bandyopadhyay, J. Sun, A. Vermeulen et al., Ibrutinib versus 382 temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, p.383

, Lancet, vol.387, pp.770-778, 2016.

J. C. Byrd, J. R. Brown, S. O'brien, J. C. Barrientos, N. E. Kay et al.,

U. Mulligan, S. Jaeger, P. M. Devereux, R. R. Barr, T. J. Furman et al.,

F. Thornton, T. Caligaris-cappio, J. Robak, S. J. Delgado, M. Schuster et al.,

A. Gill, C. Bloor, C. Dearden, J. J. Moreno, A. D. Jones et al., , p.389

P. Hillmen, Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia, N. Engl. J, vol.390

. Med, , vol.371, pp.213-236, 2014.

J. A. Burger, A. Tedeschi, P. M. Barr, T. Robak, C. Owen et al., , p.393

J. Li, D. Simpson, S. Grosicki, S. Devereux, H. Mccarthy et al., , p.394

D. A. Stevens, A. Janssens, F. Offner, J. Mayer, M. O'dwyer et al.,

C. S. Polliack, D. Tam, M. Suri, F. Cheng, L. Clow et al., Ibrutinib as initial 396 therapy for patients with chronic lymphocytic leukemia, N. Engl. J. Med, vol.373, pp.2425-2437, 2015.

M. A. Dimopoulos, J. Trotman, A. Tedeschi, J. V. Matous, D. Macdonald et al.,

M. Granell, M. A. Kyrtsonis, V. Leblond, A. Symeonidis, E. Kastritis et al.,

C. Treon and . Buske, Ibrutinib for patients with rituximab-refractory Waldenström's macroglobulinaemia 402 (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial, Lancet Oncol, vol.18, pp.241-250, 2017.

A. Noy, S. De-vos, C. Thieblemont, P. Martin, C. R. Flowers et al.,

S. Coleman, S. Peles, J. C. Smith, A. Barrientos, B. Smith et al., , p.407

, Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma, p.408

, Blood, vol.129, pp.2224-2232, 2017.

S. H. Bernstein, J. M. Unger, M. Leblanc, J. Friedberg, T. P. Miller et al., Natural history of CNS 411 relapse in patients with aggressive non-Hodgkin's lymphoma: a 20-year follow-up analysis of SWOG 412 8516, J. Clin. Oncol, vol.27, pp.114-119, 2009.

R. Nau, F. Sörgel, and H. Eiffert, Penetration of drugs through the blood-cerebrospinal fluid/blood-415 brain barrier for treatment of central nervous system infections, Clin. Microbiol. Rev, vol.23, pp.858-416, 2010.

S. Bernard, L. Goldwirt, S. Amorim, P. J. Brière, E. De-kerviler et al.,

. Thieblemont, Activity of ibrutinib in mantle cell lymphoma patients with central nervous system 420 relapse, Blood, vol.126, pp.1695-1698, 2015.

A. Cabannes-hamy, R. Lemal, L. Goldwirt, S. Poulain, R. Amorin et al.,

J. O. De-kerviler, H. Bay, K. Sauvageon, S. Beldjord, O. Mourah et al., Efficacy of 424 ibrutinib in the treatment of Bing-Neel syndrome, Am. J. Hematol, vol.91, pp.17-19, 2016.

D. L. Tucker, G. Naylor, A. Kruger, M. S. Hamilton, G. Follows et al., Ibrutinib is a safe and 427 effective therapy for systemic mantle cell lymphoma with central nervous system involvement -a 428 multi-centre case series from the United Kingdom, Br. J. Haematol, vol.178, pp.327-329, 2017.

C. Mason, S. Savona, J. N. Rini, J. J. Castillo, L. Xu et al., Ibrutinib 431 penetrates the blood brain barrier and shows efficacy in the therapy of Bing Neel syndrome, Br. J, p.432

. Haematol, , vol.179, pp.339-341, 2017.

A. Wanquet, R. Birsen, R. Lemal, M. Hunault, V. Leblond et al., Ibrutinib 435 responsive central nervous system involvement in chronic lymphocytic leukemia, Blood, vol.127, pp.436-2356, 2016.

L. S. Hiemcke-jiwa, R. J. Leguit, J. H. Radersma-van-loon, P. E. Westerweel, J. J. Rood et al.,

M. M. Doorduijn, M. C. Huibers, and . Minnema, Efficacy of ibrutinib in a patient with transformed 440 lymphoplasmacytic lymphoma and central nervous system involvement, Leuk. Lymphoma, p.1, 2017.

S. Veeraraghavan, S. Viswanadha, S. Thappali, B. Govindarajulu, S. Vakkalanka et al.,

. Rangasamy, Simultaneous quantification of lenalidomide, ibrutinib and its active metabolite PCI-445 45227 in rat plasma by LC-MS/MS: application to a pharmacokinetic study, J. Pharm. Biomed. Anal, vol.446, pp.151-158, 2015.

J. J. Rood, S. Van-hoppe, A. H. Schinkel, J. H. Schellens, J. H. Beijnen et al., Liquid 449 chromatography-tandem mass spectrometric assay for the simultaneous determination of the 450

, irreversible BTK inhibitor ibrutinib and its dihydrodiol-metabolite in plasma and its application in 451 mouse pharmacokinetic studies, J. Pharm. Biomed. Anal, vol.118, pp.123-131, 2016.

H. H. Huynh, C. Pressiat, H. Sauvageon, H. , I. Madelaine et al.,

S. Goldwirt and . Mourah, Development and Validation of a Simultaneous Quantification Method of 14

, Tyrosine Kinase Inhibitors in Human Plasma Using LC-MS/MS, vol.39, pp.43-54, 2017.

R. Vries, M. Huang, N. Bode, P. Jejurkar, J. Jong et al.,

T. Timmerman and . Verhaeghe, Bioanalysis of ibrutinib and its active metabolite in human plasma: 459 selectivity issue, impact assessment and resolution, Bioanalysis, vol.7, pp.2713-2724, 2015.

M. Fouad, M. Helvenstein, and B. Blankert, Ultra High Performance Liquid Chromatography Method 462 for the Determination of Two Recently FDA Approved TKIs in Human Plasma Using Diode Array 463

, Detection, J. Anal. Methods Chem, vol.215128, pp.1-7, 2015.

K. Dunleavy, C. E. Lai, M. Roschewski, J. N. Brudno, B. Widemann et al.,

M. Lucas, C. M. Stetler-stevenson, P. Yuan, D. Harris, J. A. Cole et al.,

. Wyndham, WilsonPhase I Study of Dose-Adjusted-Teddi-R with Ibrutinib in Untreated, p.468

C. Relapsed/refractory-primary and . Lymphoma, Blood, vol.126, pp.472-472, 2015.

C. Grommes, A. Pastore, I. Gavrilovic, I. , T. Kaley et al.,

I. Hatzoglou, L. Mellinghoff, and . Deangelis, Single-Agent Ibrutinib in Recurrent/Refractory Central 472

, Nervous System Lymphoma, Blood, vol.128, pp.783-783, 2016.

P. Hubert, J. J. Nguyen-huu, B. Boulanger, E. Chapuzet, P. Chiap et al.,

M. Dewé, M. Feinberg, M. Lallier, N. Laurentie, G. Mercier et al., Harmonization 476 of strategies for the validation of quantitative analytical procedures. A SFSTP proposal -Part I, J, p.477

, Pharm. Biomed. Anal, vol.36, pp.579-586, 2004.

P. Hubert, J. J. Nguyen-huu, B. Boulanger, E. Chapuzet, P. Chiap et al., , p.480

W. Dewé, M. Feinberg, M. Lallier, M. Laurentie, N. Mercier et al., , p.481

, Harmonization of strategies for the validation of quantitative analytical procedures. A SFSTP proposal 482 -part II, J. Pharm. Biomed. Anal, vol.45, pp.70-81, 2007.

R. Difrancesco, R. Dicenzo, G. Vicente, J. Donnelly, T. M. Martin et al.,

. Morse, Determination of lopinavir cerebral spinal fluid and plasma ultrafiltrate concentrations by 486 liquid chromatography coupled to tandem mass spectrometry, J. Pharm. Biomed. Anal, vol.4, pp.487-1139, 2007.

L. Sosvorova, J. Vitku, T. Chlupacova, M. Mohapl, and R. Hampl, Determination of seven selected 490 neuro-and immunomodulatory steroids in human cerebrospinal fluid and plasma using LC-MS/MS, p.491

, Steroids, vol.98, pp.1-8, 2015.

F. Bai, J. Johnson, F. Wang, L. Yang, A. Broniscer et al., Determination of vandetanib in 494 human plasma and cerebrospinal fluid by liquid chromatography electrospray ionization tandem 495 mass spectrometry (LC-ESI-MS/MS), J. Chromatogr. B, vol.879, pp.2561-2566, 2011.

M. Josefsson, M. Roman, E. Skogh, and M. L. Dahl, Liquid chromatography/tandem mass 498 spectrometry method for determination of olanzapine and N-desmethylolanzapine in human serum 499 and cerebrospinal fluid, J. Pharm. Biomed. Anal, vol.53, pp.576-82, 2010.

X. Yang, G. Li, L. Chen, C. Zhang, X. Wan et al., Quantitative determination of hederagenin in rat 502 plasma and cerebrospinal fluid by ultra fast liquid chromatography-tandem mass spectrometry 503 method, J. Chromatogr. B, vol.879, pp.1973-1979, 2011.

P. Voehringer, R. Fuertig, and B. Ferger, A novel liquid chromatography/tandem mass spectrometry 506 method for the quantification of glycine as biomarker in brain microdialysis and cerebrospinal fluid 507 samples within 5min, J. Chromatogr. B, vol.939, pp.92-97, 2013.

J. Jiang, C. A. James, and P. Wong, Bioanalytical method development and validation for the 510 determination of glycine in human cerebrospinal fluid by ion-pair reversed-phase liquid 511 chromatography-tandem mass spectrometry, J. Pharm. Biomed. Anal, vol.128, pp.132-140, 2016.

J. Jong, D. Skee, P. Hellemans, J. Jiao, R. Vries et al., , p.514

E. Sukbuntherng and . Mannaert, Single-dose pharmacokinetics of ibrutinib in subjects with varying 515 degrees of hepatic impairment, Leuk. Lymphoma, vol.58, pp.185-194, 2017.

E. Scheers, L. Leclercq, J. Jong, N. Bode, M. Bockx et al., , p.518

J. Sukbuntherng and G. Mannens, Absorption, metabolism, and excretion of oral 14 C radiolabeled 519 ibrutinib: an open-label, phase I, single-dose study in healthy men, Drug Metab. Dispos, vol.43, p.520, 2015.