PAREXEL Bioanalytical Laboratory Services Page 2 PAREXEL Bioanalytical Division offers a wide range of bioanalytical services. PK analysis Clinical laboratory -16 LC-MS/MS instruments – Routine safety testing (serology, Applied Bioscience API2000 haematology and clinical chemistry) to API5500 Immunochemistry laboratory -Development and validation PK/PD analysis of macromolecules of new bioanalytical assays using RIA, ELISA, ECL -More than 500 validated methods Cellular assays are performed used in over 2,500 clinical & using Flow Cytometry and preclinical trials to date Cytometric Bead Array (CBA) Preferred partnerships with accredited laboratories are in place, for specialized biomarker assays not directly provided by PAREXEL Several methods have been developed for proprietary drugs and these are not listed in this document due to confidentiality Our validation procedures and SOP’s are in compliance with the United States of America (FDA)1 and European (EMEA)2 guidelines The laboratories are GLP & ISO17025 certified and were successfully inspected by the FDA, MHRA, WHO and EMA 1 Guidance for Industry, Bioanalytical Method Validation (2001) and Workshop/Conference Report – Quantitative bioanalytical methods validation and implementation: best practices for chromatographic and ligand binding assays (Viswanathan et al., AAPS J. 2007; 9 (1) Article 4). 2 ”CPMP/EWP/QWP/1401/98, Note for Guidance on the Investigation of Bioavailability and Bioequivalence" (EMEA) Bold = Compounds that have active metabolites to be considered for analysis Blue Band = Active metabolite of the molecule referenced above in bold 2 PAREXEL Bioanalytical Laboratory Services Page 3 PAREXEL Bioanalytical Laboratory Services Page 2 Validated assay methods Storage Light Drug LLOQ Technique Matrix Temp Sensitivity Acamprosate 1.08 ng/ml LC-MS/MS Human Plasma -20 °C Normal Light Acarbose 0.32 ng/ml LC-MS/MS Human Plasma -20 °C Normal Light Acebutolol 5.56 ng/ml HPLC Fluorescence Human Plasma -20 °C Normal Light Diacetolol 20.9 ng/ml HPLC Fluorescence Human Plasma -20 °C Normal Light PAREXEL Bioanalytical Division offers Aceclofenac 25.1 ng/ml LC-MS/MS Human Plasma -20 °C Normal Light a wide range of bioanalytical services. Acetaminophen 0.16 µg/ml LC-MS/MS Human Plasma -20 °C Normal Light Acetazolamide 14.2 ng.ml LC-MS/MS Human Plasma -70 °C Normal Light Acetylsalicylic Acid 28.1 ng/ml HPLC Fluorescence Human Plasma -70 °C Normal Light PK analysis Clinical laboratory Salicylic Acid 40.0 ng/ml HPLC Fluorescence Human Plasma -70 °C Normal Light -16 LC-MS/MS instruments – Routine safety testing (serology, Applied Bioscience API2000 haematology and clinical chemistry) Acyclovir 5.03 ng/ml LC-MS/MS Human Plasma -20 °C Normal Light to API5500 α-GST 2.50 ng/ml ELISA Urine -20 °C Normal Light Immunochemistry laboratory -Development and validation PK/PD analysis of macromolecules α-GST 0.74 ng/ml ELISA Human Serum -20 °C Normal Light of new bioanalytical assays using RIA, ELISA, ECL Alfuzosin 0.34 ng/ml LC-MS/MS Human Plasma -20 °C Normal Light -More than 500 validated methods Cellular assays are performed Alendronate 1.95 ng/ml HPLC Fluorescence Urine -20 °C Normal Light used in over 2,500 clinical & using Flow Cytometry and Allopurinol 0.35 µg/ml HPLC UV Human Plasma -20 °C Normal Light preclinical trials to date Cytometric Bead Array (CBA) Oxypurinol 0.64 µg/ml HPLC UV Human Plasma -20 °C Normal Light Preferred partnerships with accredited laboratories are in place, for specialized biomarker assays not directly provided by PAREXEL Alprazolam 0.50 ng/ml GC ECD Human Plasma -20 °C Normal Light Several methods have been developed for proprietary drugs and these are not listed in this document due to confidentiality Altizide 3.03 ng/ml HPLC UV Human Plasma -20 °C Normal Light Our validation procedures and SOP’s are in compliance with the United States of America (FDA)1 and European (EMEA)2 guidelines The laboratories are GLP & ISO17025 certified and were successfully inspected by the FDA, MHRA, WHO and EMA Ambroxol 0.28 ng/ml LC-MS/MS Human Plasma -20 °C Normal Light 1 Guidance for Industry, Bioanalytical Method Validation (2001) and Workshop/Conference Report – Quantitative bioanalytical methods validation and implementation: best practices for chromatographic and ligand binding assays (Viswanathan et al., AAPS J. 2007; 9 (1) Article 4). Amiloride 0.28 ng/ml HPLC UV Human Plasma -20 °C Normal Light 2 ”CPMP/EWP/QWP/1401/98, Note for Guidance on the Investigation of Bioavailability and Bioequivalence" (EMEA) Amiodarone 1.57 ng/ml HPLC UV Human Plasma -20 °C Normal Light Bold = Compounds that have active metabolites to be considered for analysis Blue Band = Active metabolite of the molecule referenced above in bold Bold = Compounds that have active metabolites to be considered for analysis Blue Band = Active metabolite of the molecule referenced above in bold 3 PAREXEL Bioanalytical Laboratory Services Page 4 Validated assay methods Storage Light Drug LLOQ Technique Matrix Temp Sensitivity N-desethylamiodarone 6.96 ng/ml HPLC UV Human Plasma -20 °C Normal Light Amisulpride 2.40 ng/ml HPLC UV Human Plasma -20 °C Normal Light Amitriptyline 0.89 ng/ml GC NPD Human Plasma -20 °C Normal Light Amlodipine 0.05 ng/ml LC-MS/MS Human Plasma -20 °C Light Sensitive Amoxycillin 98.7 ng/ml HPLC UV Human Plasma -70 °C Normal Light Anagrelide 0.09 ng/ml LC-MS/MS Human Plasma -20 °C Normal Light Antipyrine 0.60 µg/ml HPLC UV Urine -70 °C Normal Light 4-OH-antipyrine 1.94 µg/ml HPLC UV Urine -70 °C Normal Light Nor-Antipyrine 1.05 µg/ml HPLC UV Urine -70 °C Normal Light Anti-Insulin Antibodies 200 ng/ml RIPA Human Plasma -20 °C Normal Light (semi-quantitative) (sensitivity) Atenolol 13.0 ng/ml HPLC Fluorescence Human Plasma -70 °C Normal Light Atovaquone 0.44 µg/ml HPLC UV Human Plasma -20 °C Normal Light Atropine 0.61 µg/ml LC-MS/MS Colic Mixture -20 °C Normal Light Azathioprine 0.47 ng/ml LC-MS/MS Human Plasma -70 °C Light Sensitive 6-Mercaptopurine 0.47 ng/ml LC-MS/MS Human Plasma -70 °C Light Sensitive Baclofen 35.0 ng/ml HPLC UV Human Plasma -20 °C Normal Light Benfluorex 0.39 ng/ml LC-MS/MS Human Plasma -70 °C Normal Light Norfenfluramine 0.20 ng/ml LC-MS/MS Human Plasma -70 °C Normal Light THEP 0.39 ng/ml LC-MS/MS Human Plasma -70 °C Normal Light Betamethazone 58.7 pg/ml LC-MS/MS Human Plasma -20 ºC Normal Light Bezafibrate 0.10 µg/ml HPLC UV Human Plasma -20 °C Normal Light Bold = Compounds that have active metabolites to be considered for analysis Blue Band = Active metabolite of the molecule referenced above in bold 4 PAREXEL Bioanalytical Laboratory Services Page 4 PAREXEL Bioanalytical Laboratory Services Page 5 Validated assay methods Validated assay methods Storage Light Storage Light Drug LLOQ Technique Matrix Drug LLOQ Technique Matrix Temp Sensitivity Temp Sensitivity N-desethylamiodarone 6.96 ng/ml HPLC UV Human Plasma -20 °C Normal Light Bicalutamide 30.3 ng/ml LC-MS/MS Human Plasma -70 °C Normal Light Amisulpride 2.40 ng/ml HPLC UV Human Plasma -20 °C Normal Light Bindarit 0.10 µg/ml LC-MS/MS Plasma/Urine -20 °C Normal light Amitriptyline 0.89 ng/ml GC NPD Human Plasma -20 °C Normal Light Bisoprolol 0.88 ng/ml HPLC Fluorescence Human Plasma -20 °C Normal Light Amlodipine 0.05 ng/ml LC-MS/MS Human Plasma -20 °C Light Sensitive Bromazepam 1.56 ng/ml GC ECD Human Plasma -20 °C Normal Light Amoxycillin 98.7 ng/ml HPLC UV Human Plasma -70 °C Normal Light Budesonide 20.8 pg/ml LC-MS/MS Human Plasma -70 °C Light sensitive Anagrelide 0.09 ng/ml LC-MS/MS Human Plasma -20 °C Normal Light Buflomedil 0.15 µg/ml HPLC UV Human Plasma -20 °C Normal Light Antipyrine 0.60 µg/ml HPLC UV Urine -70 °C Normal Light Bumetanide 0.39 ng/ml HPLC UV Human Plasma -20 °C Normal Light 4-OH-antipyrine 1.94 µg/ml HPLC UV Urine -70 °C Normal Light Bupropion 7.81 ng/ml LC-MS/MS Human Plasma -20 °C Normal Light Nor-Antipyrine 1.05 µg/ml HPLC UV Urine -70 °C Normal Light Hydroxybupropion 7.65 ng/ml LC-MS/MS Human Plasma -20 °C Normal Light Anti-Insulin Antibodies 200 ng/ml Cabergoline 1.50 pg/ml LC-MS/MS Human Plasma -20 °C Normal Light RIPA Human Plasma -20 °C Normal Light (semi-quantitative) (sensitivity) Caffeine 26.6 ng/ml LC-MS/MS Human Plasma -20 °C Normal Light Atenolol 13.0 ng/ml HPLC Fluorescence Human Plasma -70 °C Normal Light Paraxanthine 26.2 ng/ml LC-MS/MS Human Plasma -20 °C Normal Light Atovaquone 0.44 µg/ml HPLC UV Human Plasma -20 °C Normal Light Calanolide 22.3 ng/ml HPLC Fluorescence Human Plasma -20 °C Light Sensitive Atropine 0.61 µg/ml LC-MS/MS Colic Mixture -20 °C Normal Light Candesartan 2.49 ng/ml LC-MS/MS Human Plasma -20 °C Light Sensitive Azathioprine 0.47 ng/ml LC-MS/MS Human Plasma -70 °C Light Sensitive Capecitabine 7.81 ng/ml LC-MS/MS Human Plasma -70 °C Normal Light 6-Mercaptopurine 0.47 ng/ml LC-MS/MS Human Plasma -70 °C Light Sensitive Captopril 23.3 ng/ml HPLC UV Human Plasma -20 °C Normal Light Baclofen 35.0 ng/ml HPLC UV Human Plasma -20 °C Normal Light Carbamazepine 2.64 ng/ml LC-MS/MS Human Plasma -20 °C Normal Light Benfluorex 0.39 ng/ml LC-MS/MS Human Plasma -70 °C Normal Light Carbamazepine-10,11-epoxide 5.15 ng/ml LC-MS/MS Human Plasma -20 °C Normal Light Norfenfluramine 0.20 ng/ml LC-MS/MS Human Plasma -70 °C Normal Light Carbamazepine -10,11-diol 9.12 ng/ml HPLC UV Human Plasma -20 °C Normal Light THEP 0.39 ng/ml LC-MS/MS Human Plasma -70 °C Normal Light Carbidopa 2.30 ng/ml LC-MS/MS Human Plasma -70 °C Normal Light Betamethazone 58.7 pg/ml LC-MS/MS Human Plasma -20 ºC Normal Light Carvedilol 1.26 ng/ml LC-MS/MS Human Plasma -20 °C