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 2 1-3 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
HDPE LDPEEVA PVC 2 g10 ml 50 3 2 g 10 ml 20 ml 50 72 GC-MS HP-5MS 30 m x 0.32 mm 1.0 µm 2 ml/ 1% B 1 2.5 B 20% 30 1% B 65 APBR1800 psi 1.0 µl 5.1 220 nm MS m/z 200 1200 3 kv 25 V MS 0.1% / 0.2 ml/ Empower 3 35 51 20 320 20.75 300 1 µl 1 400 ml/ 350 m/z 1500 40 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 12 220 nm MS m/z 200 1500 30 V 3 kv Empower 2 UPC 2 2
LC GC GC LC UPC 2 1 2 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
H H P 5- -2- -4-5-Cl-2-H-4- BP Cl 4- -2-4-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
0.60 0.58 0.56 0.54 0.52 0.50 0.48 0.46 Irganox 1330 0.44 0.42 0.40 0.38 0.36 0.34 0.32 0.30 0.28 0.26 0.24 0.22 0.20 0.18 0.16 0.14 0.12 0.10 0.08 0.06 BHT 5-Cl-2-H-4- BP Tinuvin P Tinuvin 328 2-H-4- BP Uvitex B augard 445 Irganox 1010 Irganox 245 Lowinox 44B25 ACQUITY UPC 2 0.04 0.02 0.00-0.02 0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80 2.00 2.20 2.40 2.60 2.80 3.00 3.20 3.40 3.60 3.80 4.00 4.20 4.40 4.60 4.80 5.00 5.20 5.40 5.60 5.80 6.00 6.20 6.40 6.60 6.80 7.00 7.20 7.40 7.60 7.80 8.00 8.20 8.40 8.60 8.80 9.00 9.20 9.40 9.60 9.80 10.00 0.60 0.55 Date Acquired: 9/15/2012 7:48:39 AM EDT Sampleame: 14 PA mix Injection Id: 2308 0.50 0.45 0.40 0.35 0.30 0.25 0.20 0.15 0.10 0.05 0.00-0.05 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 1010-0.10-0.15 0.00 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 5.50 6.00 6.50 7.00 7.50 8.00 8.50 9.00 9.50 10.00 BHT 5-Cl-2-H-4- BP Tinuvin P Tinuvin 328 2-H-4- BP augard 445 GC-MS Uvitex B 2. UPC 2 5
Column ame: 2-EP Sampleame: PET IPA mw Date Acquired: 9/6/2012 6:14:33 PM EDT Instrument Method Id: 1953 Injection Id: 2129 0.60 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 0.40 0.20 PVC -0.005 0.00 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: 2003 0.005 EVA 0.010 EVA -0.005 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: 1992 0.010 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 0.010 HDPE -0.005 0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80 2.00 2.20 2.40 2.60 2.80 3.00 3.20 3.40 3.60 3.80 4.00 4.20 4.40 4.60 4.80 5.00 IPA 0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80 2.00 2.20 2.40 2.60 2.80 3.00 3.20 3.40 3.60 3.80 4.00 4.20 4.40 4.60 4.80 5.00 3. IPA ACQUITY UPC 2 % % % % HDPE IPA microwave 0 0 0 0 090712_018 Sm (Mn, 2x3) PVC 3.47 20.44 3.91 19.14 21.02 4.42 5.21 16.02 6.75 7.47 6.51 8.56 8.82 9.23 12.52 16.50 18.46 21.98 22.45 24.19 27.32 28.01 11.27 14.65 15.39 17.44 25.66 26.53 28.77 29.00 30.55 31.12 32.98 33.59 34.37 38.81 39.80 34.64 35.59 37.48 4.00 5.00 6.00 7.00 8.00 9.00 10.0011.0012.0013.0014.0015.0016.0017.0018.0019.0020.0021.0022.0023.0024.0025.0026.0027.0028.0029.0030.0031.0032.0033.0034.0035.0036.0037.0038.0039.00 090712_017 Sm (Mn, 2x3) EVA 3.38 25.51 19.01 20.87 22.08 22.91 24.29 26.43 26.80 32.63 1: TF MS AP+ 2.19e6 1: TF MS AP+ 2.19e6 4.00 5.00 6.00 7.00 8.00 9.00 10.0011.0012.0013.0014.0015.0016.0017.0018.0019.0020.0021.0022.0023.0024.0025.0026.0027.0028.0029.0030.0031.0032.0033.0034.0035.0036.0037.0038.0039.00 14.88 1: TF MS AP+ 090712_016 Sm (Mn, 2x3) 2.19e6 LDPE 16.35 15.27 14.07 16.44 19.4520.17 18.08 21.36 29.53 22.15 22.74 24.0524.86 25.6926.39 27.36 28.46 33.34 35.93 30.67 36.36 31.2131.94 36.81 29.95 34.06 37.58 13.73 3.42 15.58 17.44 34.79 39.45 4.55 6.56 7.52 5.10 5.43 8.24 9.13 10.47 11.01 11.9313.09 4.00 5.00 6.00 7.00 8.00 9.00 10.0011.0012.0013.0014.0015.0016.0017.0018.0019.0020.0021.0022.0023.0024.0025.0026.0027.0028.0029.0030.0031.0032.0033.0034.0035.0036.0037.0038.0039.00 090712_015 Sm (Mn, 2x3) 1: TF MS AP+ 2.19e6 HDPE 3.73 16.52 18.32 4.59 5.83 6.24 7.37 8.108.42 17.57 6.79 9.75 10.96 13.62 14.11 15.83 11.66 12.49 15.39 18.91 20.73 20.45 22.1622.93 23.60 24.65 25.58 26.56 27.08 27.41 28.54 29.71 30.50 31.4731.73 33.46 34.2734.60 36.3936.75 37.94 39.39 38.55 4.00 5.00 6.00 7.00 8.00 9.00 10.0011.0012.0013.0014.0015.0016.0017.0018.0019.0020.0021.0022.0023.0024.0025.0026.0027.0028.0029.0030.0031.0032.0033.0034.0035.0036.0037.0038.0039.00 0% 0% 0% 0% HDPE hexane microwave 3.12 3.00 090712_007 Sm (Mn, 2x3) PVC EVA LDPE HDPE 7.64 8.26 8.51 9.91 10.19 10.60 11.45 15.46 14.70 14.43 13.73 16.02 16.21 17.57 18.60 18.76 19.48 19.90 20.53 24.93 22.13 23.92 24.25 22.33 23.43 1: TF MS AP+ 2.14e6 4.00 5.00 6.00 7.00 8.00 9.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 27.00 28.00 29.00 30.00 31.00 32.00 33.00 34.00 35.00 36.00 37.00 38.00 39.00 090712_006 Sm (Mn, 2x3) 17.90 3.69 4.60 5.40 5.66 6.44 7.79 8.55 9.27 9.85 10.72 11.32 14.27 17.77 12.51 13.39 15.57 17.09 1: TF MS AP+ 2.14e6 4.00 5.00 6.00 7.00 8.00 9.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 27.00 28.00 29.00 30.00 31.00 32.00 33.00 34.00 35.00 36.00 37.00 38.00 39.00 090712_005 Sm (Mn, 2x3) 3.36 4.90 4.19 5.12 6.07 6.93 7.76 8.70 16.35 9.13 10.09 10.64 13.04 14.87 15.36 16.67 11.72 13.51 1: TF MS AP+ 2.14e6 4.00 5.00 6.00 7.00 8.00 9.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 27.00 28.00 29.00 30.00 31.00 32.00 33.00 34.00 35.00 36.00 37.00 38.00 39.00 090712_004 Sm (Mn, 2x3) 18.31 3.00 7.19 7.52 8.23 4.32 4.94 5.28 9.43 12.30 12.99 13.87 14.42 18.07 6.20 9.90 11.20 15.57 15.88 4.02 1: TF MS AP+ 2.14e6 4.00 5.00 6.00 7.00 8.00 9.00 10.00 11.00 12.00 13.00 14.00 15.00 16.00 17.00 18.00 19.00 20.00 21.00 22.00 23.00 24.00 25.00 26.00 27.00 28.00 29.00 30.00 31.00 32.00 33.00 34.00 35.00 36.00 37.00 38.00 39.00 25.18 25.36 28.84 29.24 27.46 27.73 20.74 23.74 26.33 29.28 19.36 19.77 25.23 29.71 21.66 23.09 23.91 27.38 28.29 30.86 22.84 31.29 20.25 18.52 18.7519.53 20.08 19.46 20.51 21.94 22.45 21.79 23.25 30.47 31.21 32.47 33.76 34.86 36.16 36.48 38.35 39.04 39.81 32.34 24.30 24.87 25.82 29.38 29.82 30.56 33.38 27.10 27.81 31.46 31.86 26.30 27.76 21.68 22.56 24.03 26.05 26.78 28.71 29.71 30.24 30.96 32.71 34.83 37.02 37.77 38.30 33.75 36.18 33.63 35.38 35.73 36.73 38.96 37.86 39.75 39.59 33.88 34.93 31.98 33.07 36.43 36.17 37.29 37.67 39.06 39.36 IPA 4. IPA GC-MS ACQUITY UPC 2 5 Irganox 1010 3 LDPE MS 6 7 LDPE IPA 0.050 0.048 0.046 0.044 0.042 0.040 0.038 0.036 0.034 0.032 Irganox 1010 0.030 0.028 0.026 0.024 0.022 0.020 0.018 0.016 0.014 0.012 0.010 0.008 0.006 0.004 0.002-0.002-0.004-0.006-0.008 0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80 2.00 2.20 2.40 2.60 2.80 3.00 3.20 3.40 3.60 3.80 4.00 4.20 4.40 4.60 4.80 5.00 Minutes 5. ACQUITY UPC 2 LDPE UPC 2 6
2.0x10 7 Combined - SQ 1: MS Scan 1: 200.00-1200.00 ES+, Centroid, CV=Tune 548.6 1.8x10 7 3.5x10 6 3.0x10 6 2.5x10 6 2.0x10 6 1.5x10 6 1.0x10 6 Intensity 1.6x10 7 1.4x10 7 1.2x10 7 1.0x10 7 549.6 8.0x10 6 6.0x10 6 475.5 4.0x10 6 553.6 531.6 2.0x10 6 476.5 554.6 569.5 0.0 450.00 460.00 470.00 480.00 490.00 500.00 510.00 520.00 530.00 540.00 550.00 560.00 570.00 580.00 590.00 600.00 m/z 5.0x10 5 0.0 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 6. UPC 2 LDPE Irganox1076 2.2x10 7 Combined - SQ 1: MS Scan 1: 200.00-1200.00 ES+, Centroid, CV=Tune 548.6 2.0x10 7 1.0x10 7 1.8x10 7 1.6x10 7 8.0x10 6 6.0x10 6 4.0x10 6 Intensity 1.4x10 7 1.2x10 7 1.0x10 7 549.6 475.5 8.0x10 6 553.6 6.0x10 6 4.0x10 6 476.5 531.6 554.6 572.6 2.0x10 6 0.0 450.00 460.00 470.00 480.00 490.00 500.00 510.00 520.00 530.00 540.00 550.00 560.00 570.00 580.00 590.00 600.00 m/z 2.0x10 6 0.0 0.50 1.00 1.50 2.00 2.50 3.00 3.50 4.00 4.50 5.00 7. UPC 2 GC-MS UPC 2 7
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. 2011 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). 1999 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, 96-99. 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. 20138 720004490JAPDF