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RITUXIMAB ELISA (MAB-BASED)
Enzyme immunoassay for the specific and quantitative determination of free Rituximab (Rituxan®, Mabthera®) in serum and plasma.
The solid phase (MTP) is coated by a highly specific monoclonal antibody directed against Rituximab. Therefore any cross reactivity to the other therapeutical monoclonal antibodies is excluded.
| Required Volume (µL) | 10 |
| Incubation Time (min) | 100 |
| Sample | Serum or Plasma |
| Plate Size | 96 Tests |
| Standard Range (ng/mL, 10x) | 0-2000 |
| Detection Limit (ng/mL) | 5 |
| Spike Recovery (%) | >95 |
| Shelf Life (years) | 2 |
Intended Use: This kit has been developed for the measurement of drug levels in research and diagnostic uses. It is suitable for Therapeutical Drug Monitoring (TDM) purposes.
Rituxan® and Mabthera® are trademarks of Biogen Idec/Genentech Inc.
ESSAY CHARACTERISTICS
SPECIFICITY
There is no cross reaction with any other proteins present in native human serum. A screening test was performed with 48 different native human sera. All produced OD450/620 nm values less than the mean OD (0.204) of standard D (6 ng/mL). In addition, binding of Rituximab is inhibited by recombinant human CD20 protein. Therefore, the ImmunoGuide Rituximab ELISA (mAb-Based) measures the biologically active free form of Rituximab, i.e. not pre-occupied by human CD20 antigen. No cross reaction was observed with sera spiked with the other therapeutic antibodies including Infliximab, Adalimumab, Golimumab, Etanercept, Bevacizumab and Trastuzumab at concentrations up to 500 µg/mL.
SENSITIVITY
The lowest detectable level that can be clearly distinguished from the zero standard is 2 ng/mL (zero standard +2SD read from the curve) under the above-described conditions. Analytical sensitivity is 2 ng/mL, and corresponding to the detection limit (limit of quantification) of 4 µg/mL for undiluted clinical samples because the serum or plasma samples are instructed to be diluted at 1:2000 before starting the assay.
PRECISION
Intra-assay CV: <10%.
Inter-assay CV: <10%.
RECOVERY
Recovery rate was found to be >95% with native human serum and plasma samples when spiked with exogenous Rituximab.
AUTOMATION
The ImmunoGuide Rituximab ELISA (mAb-based) is suitable also for being used by an automated ELISA processor.
REFERENCES
1. Assouline S, Buccheri V, Delmer A, Gaidano G, McIntyre C, Brewster M, Catalani O, Hourcade-Potelleret F, Sayyed P, Badoux X. Pharmacokinetics and safety of subcutaneous rituximab plus fludarabine and cyclophosphamide for patients with chronic lymphocytic leukaemia. Br J Clin Pharmacol. 2015;80(5):1001-9
2. Salar A, Avivi I, Bittner B, Bouabdallah R, Brewster M, Catalani O, Follows G, Haynes A, Hourcade-Potelleret F, Janikova A, Larouche JF, McIntyre C, Pedersen M, Pereira J, Sayyed P, Shpilberg O, Tumyan G. Comparison of subcutaneous versus intravenous administration of rituximab as maintenance treatment for follicular lymphoma: results from a two-stage, phase IB study. J Clin Oncol. 2014;32(17):1782-91.
3. Compagno N, Cinetto F, Semenzato G, Agostini C. Subcutaneous immunoglobulin in lymphoproliferative disorders and rituximab-related secondary hypogammaglobulinemia: a single-center experience in 61 patients. Haematologica. 2014;99(6):1101-6.
4. Davies A, Merli F, Mihaljevic B, Siritanaratkul N, Solal-Céligny P, Barrett M, Berge C, Bittner B, Boehnke A, McIntyre C, Macdonald D. Pharmacokinetics and safety of subcutaneous rituximab in follicular lymphoma (SABRINA): stage 1 analysis of a randomised phase 3 study. Lancet Oncol. 2014;15(3):343-52.
5. Bittner B, Richter WF, Hourcade-Potelleret F, Herting F, Schmidt J. Non-clinical pharmacokinetic/pharmacodynamic and early clinical studies supporting development of a novel subcutaneous formulation for the monoclonal antibody rituximab. Drug Res (Stuttg). 2014;64(11):569-75.
6. Mao CP, Brovarney MR, Dabbagh K, Birnböck HF, Richter WF, Del Nagro CJ. Subcutaneous versus intravenous administration of rituximab: pharmacokinetics, CD20 target coverage and B-cell depletion in cynomolgus monkeys. PLoS One. 2013 Nov 12;8(11):e80533. doi: 10.1371/journal.pone.0080533
7. Barth MJ, Goldman S, Smith L, Perkins S, Shiramizu B, Gross TG, Harrison L, Sanger W, Geyer MB, Giulino-Roth L, Cairo MS. Rituximab pharmacokinetics in children and adolescents with de novo intermediate and advanced mature B-cell lymphoma/leukaemia: a Children's Oncology Group report. Br J Haematol. 2013;162(5):678-83.
8. Brown JR, Messmer B, Werner L, Davids MS, Mikler E, Supko JG, Fisher DC, LaCasce AS, Armand P, Jacobsen E, Dalton V, Tesar B, Fernandes SM, McDonough S, Ritz J, Rassenti L, Kipps TJ, Neuberg D, Freedman AS. A phase I study of escalated dose subcutaneous alemtuzumab given weekly with rituximab in relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma. Haematologica. 2013;98(6):964-70.
9. Gao B, Yeap S, Clements A, Balakrishnar B, Wong M, Gurney H. Evidence for therapeutic drug monitoring of targeted anticancer therapies. J Clin Oncol. 2012;30(32):4017-25.
10. Jäger U, Fridrik M, Zeitlinger M, Heintel D, Hopfinger G, Burgstaller S, Mannhalter C, Oberaigner W, Porpaczy E, Skrabs C, Einberger C, Drach J, Raderer M, Gaiger A, Putman M, Greil R; Arbeitsgemeinschaft Medikamentöse Tumortherapie (AGMT) Investigators. Rituximab serum concentrations during immuno-chemotherapy of follicular lymphoma correlate with patient gender, bone marrow infiltration and clinical response. Haematologica. 2012;97(9):1431-8.
11. McDonald V1, Manns K, Mackie IJ, We are recommending that each laboratory determines the best initial dilution for their samples in order to minimize retesting., Scully MA. Rituximab pharmacokinetics during the management of acute idiopathic thrombotic thrombocytopenic purpura. J Thromb Haemost. 2010;8(6):1201-8.
12. Tobinai K, Igarashi T, Itoh K, Kobayashi Y, Taniwaki M, Ogura M, Kinoshita T, Hotta T, Aikawa K, Tsushita K, Hiraoka A, Matsuno Y, Nakamura S, Mori S, Ohashi Y; IDEC-C2B8 Japan Study Group. Japanese multicenter phase II and pharmacokinetic study of rituximab in relapsed or refractory patients with aggressive B-cell lymphoma. Ann Oncol. 2004;15(5):821-30.
13. Alexandru S, Gonzalez E, Grande C, Hernandez A, Morales E, Praga M, Andres A, Morales JM. Monotherapy rapamycin in renal transplant recipients with lymphoma successfully treated with rituximab. Transplant Proc. 2009;41(6):2435-7.
14. Miranda-Hernández MP, López-Morales CA, Ramírez-Ibáñez ND, Piña-Lara N, Pérez NO, Molina-Pérez A, Revilla-Beltri J, Flores-Ortiz LF, Medina-Rivero E. Assessment of physicochemical properties of rituximab related to its immunomodulatory activity. J Immunol Res. 2015;2015:910763. doi: 10.1155/2015/910763
15. Mazilu D, Opriş D, Gainaru C, Iliuta M, Apetrei N, Luca G, Borangiu A, Gudu T, Peltea A, Groseanu L, Constantinescu C, Saulescu I, Bojinca V, Balanescu A, Predeteanu D, Ionescu R. Monitoring drug and antidrug levels: a rational approach in rheumatoid arthritis patients treated with biologic agents who experience inadequate response while being on a stable biologic treatment. Biomed Res Int. 2014;2014:702701. doi: 10.1155/2014/702701.
16. Mok CC. Rituximab for the treatment of rheumatoid arthritis: an update. Drug Des Devel Ther. 2013;8:87-100.
17. Chen K, Page JG, Schwartz AM, Lee TN, DeWall SL, Sikkema DJ, Wang C. False-positive immunogenicity responses are caused by CD20+ B cell membrane fragments in an anti-ofatumumab antibody bridging assay. J Immunol Methods. 2013;394(1-2):22-31.
18. Schmidt E, Hennig K, Mengede C, Zillikens D, Kromminga A. Immunogenicity of rituximab in patients with severe pemphigus. Clin Immunol. 2009;132(3):334-41.
19. Annibali O, Chiodi F, Sarlo C, Cortes M, Quaranta-Leoni FM, Quattrocchi C, Bianchi A, Bonini S, Avvisati G Rituximab as Single Agent in Primary MALT Lymphoma of the Ocular Adnexa. Biomed Res Int. 2015;2015:895105. doi: 10.1155/2015/895105.
20. Kidd DP. Rituximab is effective in severe treatment-resistant neurological Behçet's syndrome. J Neurol. 2015 Sep 26. (Epub ahead of print).
INSTRUCTIONS FOR USE
SAFETY DATA SHEET
BATCH/LOT INFORMATION