UPC 2 Baiba Cabovska, Michael D. Jones, and Andrew Aubin Waters Corporation, Milford, MA, USA UPC 2 ACQUITY UPC 2TM ACQUITY SQD Empower 3 UPC GC

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1 UPC 2 Baiba Cabovska, Michael D. Jones, and Andrew Aubin Waters Corporation, Milford, MA, USA UPC 2 ACQUITY UPC 2TM ACQUITY SQD Empower 3 UPC GC LC GC UltraPerformance Convergence Chromatography UPC 2 SFC HDPE LDPEEVA PVC 4 14 IPA IPA GC-MS IPA ACQUITY UPLC ACQUITY UPC 2 3 UPC 2 GC UPLC UPC 2 SFC UltraPerformance Convergence Chromatography TM 1

2 HDPE LDPEEVA PVC 2 g10 ml g 10 ml 20 ml GC-MS HP-5MS 30 m x 0.32 mm 1.0 µm 2 ml/ 1% B B 20% 30 1% B 65 APBR1800 psi 1.0 µl nm MS m/z kv 25 V MS 0.1% / 0.2 ml/ Empower µl ml/ 350 m/z MassLynx v4.1 UPLC A B ACQUITY UPLC ACQUITY UPLC BEH 2.1 x mm1.7 µm 0.1% / 0.1% / 0.9 ml/ 10 B 50% 90% 50% B UPC 2 ACQUITY UPC 2 PDA SQD ACQUITY UPC 2 BEH 2-EP 3.0 x mm1.7 µm A C2 B 1:1 / 2.0 ml/ 50 2 µl nm MS m/z V 3 kv Empower 2 UPC 2 2

3 LC GC GC LC UPC UPLC UPC 2 14 UPC 2 UPLC UPLC UPC 2 Irganox 1010 Irganox 245 GC-MS GC-MS Uvitex B GC LC UPC 2 UPLC UPC 2 IPA 2 3 LDPE UPLC IPA UPC 2 UPLC UPLC UPC 2 GC-MS GC-MS 4 UPC 2 3

4 H H P Cl-2-H-4- BP Cl H-2- BP S Uvitex B H H H Irganox 245 H H H H H H H H H Irganox 1330 Irganox 1010 H H Lowinox 44B25 H H Tinuvin 328 BHT augard 445 Tinuvin P 1. UPC 2 4

5 Irganox BHT 5-Cl-2-H-4- BP Tinuvin P Tinuvin H-4- BP Uvitex B augard 445 Irganox 1010 Irganox 245 Lowinox 44B25 ACQUITY UPC Date Acquired: 9/15/2012 7:48:39 AM EDT Sampleame: 14 PA mix Injection Id: Tinuvin P 5-Cl-2-H-4- BP BHT Irganox 245 Lowinox 44B25 2-H-4-4-H-2-octyloxy BP BP Uvitex B augard 445 Tinuvin 328 ACQUITY UPLC Irganox 1330 Irganox BHT 5-Cl-2-H-4- BP Tinuvin P Tinuvin H-4- BP augard 445 GC-MS Uvitex B 2. UPC 2 5

6 Column ame: 2-EP Sampleame: PET IPA mw Date Acquired: 9/6/2012 6:14:33 PM EDT Instrument Method Id: 1953 Injection Id: Column ame: 2-EP Sampleame: PET hex mw Date Acquired: 9/6/2012 4:10:57 PM EDT Instrument Method Id: 1953 Injection Id: 2014 PVC PVC Column ame: 2-EP Sampleame: EVA IPA mw Date Acquired: 9/6/2012 6:02:46 PM EDT Instrument Method Id: 1953 Injection Id: 2118 Column ame: 2-EP Sampleame: EVA hex mw Date Acquired: 9/6/2012 3:59:11 PM EDT Instrument Method Id: 1953 Injection Id: EVA EVA Column ame: 2-EP Sampleame: LDPE IPA mw Date Acquired: 9/6/2012 5:50:59 PM EDT Instrument Method Id: 1953 Injection Id: 2107 Column ame: 2-EP Sampleame: LDPE hex mw Date Acquired: 9/6/2012 3:47:25 PM EDT Instrument Method Id: 1953 Injection Id: LDPE 0.02 LDPE 0.00 Column ame: 2-EP Sampleame: HDPE IPA mw Date Acquired: 9/6/2012 5:39:12 PM EDT Instrument Method Id: 1953 Injection Id: 2096 Column ame: 2-EP Sampleame: HDPE hex mw Date Acquired: 9/6/2012 3:35:37 PM EDT Instrument Method Id: 1953 Injection Id: 1981 HDPE HDPE IPA IPA ACQUITY UPC 2 % % % % HDPE IPA microwave _018 Sm (Mn, 2x3) PVC _017 Sm (Mn, 2x3) EVA : TF MS AP+ 2.19e6 1: TF MS AP+ 2.19e : TF MS AP _016 Sm (Mn, 2x3) 2.19e6 LDPE _015 Sm (Mn, 2x3) 1: TF MS AP+ 2.19e6 HDPE % 0% 0% 0% HDPE hexane microwave _007 Sm (Mn, 2x3) PVC EVA LDPE HDPE : TF MS AP+ 2.14e _006 Sm (Mn, 2x3) : TF MS AP+ 2.14e _005 Sm (Mn, 2x3) : TF MS AP+ 2.14e _004 Sm (Mn, 2x3) : TF MS AP+ 2.14e IPA 4. IPA GC-MS ACQUITY UPC 2 5 Irganox LDPE MS 6 7 LDPE IPA Irganox Minutes 5. ACQUITY UPC 2 LDPE UPC 2 6

7 2.0x10 7 Combined - SQ 1: MS Scan 1: ES+, Centroid, CV=Tune x x x x x x x10 6 Intensity 1.6x x x x x x x x m/z 5.0x UPC 2 LDPE Irganox x10 7 Combined - SQ 1: MS Scan 1: ES+, Centroid, CV=Tune x x x x x x x10 6 Intensity 1.4x x x x x x x m/z 2.0x UPC 2 GC-MS UPC 2 7

8 ACQUITY UPC 2 LC GC UPC 2 GC UPC 2 UPLC 1/2GC 1/8 1. Balogh MP. Testing the Critical Interface: Leachables and Extractables. LCGC June. 2. Containers Closure Systems for Packaging Human Drugs and Biologics. Guidance for Industry; U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) and Center for Biologics Evaluation and Research (CBER) May. 3. orwood DL, Fenge Q. Strategies for the analysis of pharmaceutical excipients and their trace level impurities. Am Pharm Rev. 2004; 7 (5) : 92,94, MS WatersACQUITYACQUITY UPLCUPC 2 EmpowerMassLynx The Science of Whats Possible Waters Corporation ACQUITY UPC 2 UltraPerformance Convergence Chromatography Waters Corporation 2013 Waters Corporation. Printed in Japan JAPDF

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ACQUITY UPC 2 ACQUITY UPC 2 A A+D3 D ml E 10 ml K μm K μm PDA ACQUITY UPC 2 BEH mm, 1.7 μm ACQUITY UPC 2 HSS C 18 SB 3. UPC 2 Andrew Aubin Waters Corporation, Milford, MA, USA Waters ACQUITY UPC 2TM 6 tert- UltraPerformance Convergence Chromatography TM UPC 2 ACQUITY UPC 2 1 A A D3 E D3 K1 K2 UPC 2 A E K1 ACQUITY UPC 2

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