Data supplement for:

Mass Spectrometry-Based Quantification of Drug Metabolizing Enzymes – CYP and UGT Enzymes in the Beagle Dog Liver and Intestine

Aki T. Heikkinen, Arno Friedlein, Mariette Matondo, Oliver J.D. Hatley, Jens Lamerz,Aleksanteri Petsalo,Risto Juvonen, Aleksandra Galetin, Amin Rostami-Hodjegan, RuediAebersold,Tom Dunkley, Paul Cutler, Neil Parrott

This data supplement includes illustrative figures of CYP and UGT abundance and activity, technical details of the SRM assays used in the current study and a comparison of CYP abundance measurement results in the samples included in both current and earlier (Heikkinen, A.T. et al 2012, Pharm Res 29, 1832-1842) studies. The abundance of CYP and UGT enzymes in all samples are given in tabulated form as a separate Excel file.

List of Figures

Figure 1-S. Pie chart presentation of CYP and UGT abundance in beagle dog liver microsomes. 100% corresponds to sum of CYPs, sum of UGTs and sum of CYPs and UGTs quantified in the current study in charts A, B and C, respectively.

Figure 3-S. Abundance of CYP and UGT enzymes along the intestine relative to sum of all CYPs and UGTs quantified in the sample. The boxes represent the interquartile range, horizontal line is the median and the whiskers show the lowest and highest values. Solid lines are drawn through the medians to visualize the profile along the intestine. Segment numbering starts from the proximal intestine and numbers 1-5 and 6 refer to small intestine and colon, respectively. Note! y-axis is in linear scale.

Figure 4-S. Abundance of CYP enzymes along the intestine relative to sum of all CYPs quantified in the sample. The boxes represent the interquartile range, horizontal line is the median and the whiskers show the lowest and highest values. Solid lines are drawn through the medians to visualize the profile along the intestine. Segment numbering starts from the proximal intestine and numbers 1-5 and 6 refer to small intestine and colon, respectively. Note! y-axis is in linear scale.

Figure 5-S. Abundance of UGT enzymes along the intestine relative to sum of all UGTs quantified in the sample. The boxes represent the interquartile range, horizontal line is the median and the whiskers show the lowest and highest values. Solid lines are drawn through the medians. Segment numbering starts from the proximal intestine and numbers 1-5 and 6 refer to small intestine and colon, respectively. Note! y-axis is in logarithmic scale.

Figure 6-S. Abundance of microsomal protein along the intestine per g (black) and per cm (gray) tissue. The boxes represent the interquartile range, horizontal line is the median and the whiskers show the lowest and highest values. Solid lines are drawn through the medians to visualize the profile along the intestine. Segment numbering starts from the proximal intestine and numbers 1-5 and 6 refer to small intestine and colon, respectively.

Figure 7-S. Comparison of CYP quantification results in the same dog microsome samples measured in the current study and an earlier study. Solid and dashed lines show the unity line and 2 fold difference.

Figure 8-S.CYP and UGT abundance in the beagle dog liver samples. In each panel the y-axis is the log transformed enzyme abundance in dog liver homogenates (DLH) or dog liver microsomes (DLM). On the right side of the figures, the fitted line represents theoretical quantiles of the normal distribution fitted to the data. As the data is log transformed, deviations of observations from the fitted line represent deviations from log-normal distribution.

List of Tables

Table 1-S. Abundance of CYP enzymes (pmol/mg protein) measured in the current and earlier study in the same beagle dog microsome samples.

Table 2-S. SRM transitions and collision energies used for beagle dog CYP and UGT quantification.

Figure 1-S.Pie chart presentation of CYP and UGT abundance in beagle dog liver microsomes. 100% corresponds to sum of CYPs, sum of UGTs and sum of CYPs and UGTs quantified in the current study in charts A, B and C, respectively.

Figure 3-S.Abundance of CYP and UGT enzymes along the intestine relative to sum of all CYPs and UGTs quantified in the sample. The boxes represent the interquartile range, horizontal line is the median and the whiskers show the lowest and highest values. Solid lines are drawn through the medians to visualize the profile along the intestine. Segment numbering starts from the proximal intestine and numbers 1-5 and 6 refer to small intestine and colon, respectively. Note!y-axis is in linear scale.

Figure 4-S. Abundance of CYP enzymes along the intestine relative to sum of all CYPs quantified in the sample. The boxes represent the interquartile range, horizontal line is the median and the whiskers show the lowest and highest values. Solid lines are drawn through the medians to visualize the profile along the intestine. Segment numbering starts from the proximal intestine and numbers 1-5 and 6 refer to small intestine and colon, respectively. Note!y-axis is in linear scale.

Figure 5-S. Abundance of UGT enzymes along the intestine relative to sum of all UGTs quantified in the sample. The boxes represent the interquartile range, horizontal line is the median and the whiskers show the lowest and highest values. Solid lines are drawn through the medians. Segment numbering starts from the proximal intestine and numbers 1-5 and 6 refer to small intestine and colon, respectively. Note!y-axis is in logarithmic scale.

Figure 6-S. Abundance of microsomal protein along the intestine per g (black) and per cm (gray) tissue. The boxes represent the interquartile range, horizontal line is the median and the whiskers show the lowest and highest values. Solid lines are drawn through the medians to visualize the profile along the intestine. Segment numbering starts from the proximal intestine and numbers 1-5 and 6 refer to small intestine and colon, respectively.

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Data supplement for:

Mass Spectrometry-Based Quantification of Drug Metabolizing Enzymes – CYP and UGT Enzymes in the Beagle Dog Liver and Intestine

Aki T. Heikkinen, Arno Friedlein, Mariette Matondo, Oliver J.D. Hatley, Jens Lamerz,Aleksanteri Petsalo,Risto Juvonen, Aleksandra Galetin, Amin Rostami-Hodjegan, RuediAebersold,Tom Dunkley, Paul Cutler, Neil Parrott

Table 1-S. Abundance of CYP enzymes (pmol/mg protein) measured in the current and earlier study in the same beagle dog microsome samples.

Study / Current study / Heikkinen et al 2012, PharmRes 29, 1832-1842
Sample / Small intestine segment 4 / Liver / Small intestine segment 4 / Liver
Donor / M1 / M2 / F 1 / F 2 / M 1 / M 2 / F 1 / F 2 / M1 / M2 / F 1 / F 2 / M 1 / M 2 / F 1 / F 2
CYP1A2 / Protein / 36 / 171 / 78 / 23 / 96 / 50
EAEALLSR / 84 / 42 / 80 / 42
SVQDITGALLK / 36 / 171 / 78 / 26 / 116 / 60
FLTADGTTINK / 20 / 17
CYP2B11 / Protein / 2.5 / 5.4 / 1.8 / 2.1 / 42 / 64 / 81 / 49 / 3.6 / 6.3 / 1.5 / 33 / 59 / 77 / 56
QVYNNLQEIK / 1.9 / 4.0 / 1.4 / 1.8 / 33 / 40 / 66 / 38 / 3.5 / 30 / 44 / 60 / 39
DFIDAYLIR / 4.1 / 9.5 / 2.8 / 3.4 / 71 / 114 / 131 / 70 / 1.6 / 3.3 / 1.6 / 2.2 / 36 / 55 / 74 / 47
NLIDTALSLFFAGTETTSTTLR / 3.7 / 6.4 / 1.6 / 33 / 59 / 77 / 56
EALVDNAEAFSGR / 2.0 / 4.2 / 1.6 / 1.5 / 31 / 58 / 60 / 45 / 2.6 / 0.8 / 14 / 23 / 38 / 26
CYP2C21 / Protein / 45 / 119 / 70 / 64 / 27 / 41 / 37 / 36
FSLTVLR / 22 / 57 / 34 / 42 / 21 / 31 / 25 / 29
DFIDYFLIK / 72 / 177 / 141 / 62 / 36 / 49 / 61 / 39
YGLLVLLK / 57 / 170 / 71 / 100 / 26 / 46 / 34 / 42
CYP2D15 / Protein / 25 / 70 / 106 / 89 / 32 / 46 / 82 / 66
VQQEIDEVIGR / 24 / 50 / 76 / 60 / 31 / 44 / 78 / 63
GTTLITNLSSVLK / 34 / 47 / 86 / 65 / 31 / 44 / 78 / 63
DTEVQGFLIPK / 18 / 144 / 185 / 180 / 35 / 51 / 92 / 74
CYP2E1 / Protein / 44 / 85 / 70 / 51 / 39 / 66 / 63 / 46
GEVFAFQSHK / 30 / 51 / 42 / 33 / 30 / 56 / 53 / 39
GITFNNGPGWK / 23 / 44 / 37 / 27 / 28 / 43 / 43 / 33
EIPFLLEALR / 126 / 271 / 224 / 143 / 69 / 120 / 113 / 81
CYP3A12 / Protein / 9.2 / 9.6 / 5.7 / 5.6 / 83 / 77 / 272 / 69 / 7.4 / 8.4 / 4.5 / 5.2 / 71 / 70 / 193 / 63
LQEEIDATFPNK (3A12/26) / 11.4 / 16.5 / 7.3 / 7.6 / 98 / 121 / 311 / 110 / 8.4 / 10.3 / 4.8 / 6.2 / 86 / 87 / 243 / 78
DVEISGVFIPK (3A12/26) / 4.2 / 5.8 / 3.7 / 3.1 / 12 / 22 / 44 / 20 / 24 / 27 / 64 / 25
LNAQGIIQPEKPIVLK / 9.2 / 9.6 / 5.7 / 5.6 / 83 / 77 / 272 / 69 / 7.4 / 8.4 / 4.5 / 5.2 / 71 / 70 / 193 / 63
CYP3A26 / Protein / 1.2 / 1.9 / 4.6 / 2.0 / 1.7 / 1.8 / 4.8 / 1.8
GIIQPEKPVVLK / 1.2 / 1.9 / 4.6 / 2.0 / 1.7 / 1.8 / 4.8 / 1.8

1(12)

Data supplement for:

Mass Spectrometry-Based Quantification of Drug Metabolizing Enzymes – CYP and UGT Enzymes in the Beagle Dog Liver and Intestine

Aki T. Heikkinen, Arno Friedlein, Mariette Matondo, Oliver J.D. Hatley, Jens Lamerz,Aleksanteri Petsalo,Risto Juvonen, Aleksandra Galetin, Amin Rostami-Hodjegan, RuediAebersold,Tom Dunkley, Paul Cutler, Neil Parrott

Figure 7-S. Comparison of CYP quantification results in the same dog microsome samples measured in the current study and an earlier study. Solid and dashed lines show the unity line and 2 fold difference.

Figure 8-S.CYP and UGT abundance in the beagle dog liver samples. In each panel the y-axis is the log transformed enzyme abundance in dog liver homogenates (DLH) or dog liver microsomes (DLM). On the right side of the figures, the fitted line represents theoretical quantiles of the normal distribution fitted to the data. As the data is log transformed, deviations of observations from the fitted line represent deviations from log-normal distribution.

Figure 7-S. Continued

Table 2-S. SRM transitions and collision energies used for beagle dog CYP and UGT quantification.

ProteinName / PeptideSequence / FragmentIon / PrecursorCharge / light PrecursorMz / light ProductMz / ProductCharge / heavy PrecursorMz / heavy ProductMz / CollisionEnergy / Notes
CYP1A2 / EAEALLSR / y6 / 2 / 444.74 / 688.40 / 1 / 449.75 / 698.41 / 16.2 / Affected by a known gene polymorphism. Quantitation data not used for protein quantitation.
CYP1A2 / EAEALLSR / y4 / 2 / 444.74 / 488.32 / 1 / 449.75 / 498.33 / 16.2
CYP1A2 / EAEALLSR / y3 / 2 / 444.74 / 375.24 / 1 / 449.75 / 385.24 / 16.2
CYP1A2 / SVQDITGALLK / y9 / 2 / 572.83 / 958.56 / 1 / 576.84 / 966.57 / 20.1
CYP1A2 / SVQDITGALLK / y8 / 2 / 572.83 / 830.50 / 1 / 576.84 / 838.51 / 20.1
CYP1A2 / SVQDITGALLK / y6 / 2 / 572.83 / 602.39 / 1 / 576.84 / 610.40 / 20.1
CYP1A2 / FLTADGTTINK / y9 / 2 / 590.81 / 920.47 / 1 / 594.82 / 928.48 / 20.6 / Affected by a known gene polymorphism. Quantitation data not used for protein quantitation.
CYP1A2 / FLTADGTTINK / y8 / 2 / 590.81 / 819.42 / 1 / 594.82 / 827.43 / 20.6
CYP1A2 / FLTADGTTINK / y7 / 2 / 590.81 / 748.38 / 1 / 594.82 / 756.40 / 20.6
CYP2E1 / GEVFAFQSHK / y7 / 2 / 575.29 / 864.44 / 1 / 579.30 / 872.45 / 20.2
CYP2E1 / GEVFAFQSHK / y6 / 2 / 575.29 / 717.37 / 1 / 579.30 / 725.38 / 20.2
CYP2E1 / GEVFAFQSHK / y5 / 2 / 575.29 / 646.33 / 1 / 579.30 / 654.34 / 20.2
CYP2E1 / GITFNNGPGWK / y7 / 2 / 595.80 / 772.37 / 1 / 599.81 / 780.39 / 20.8
CYP2E1 / GITFNNGPGWK / y6 / 2 / 595.80 / 658.33 / 1 / 599.81 / 666.34 / 20.8
CYP2E1 / GITFNNGPGWK / y4 / 2 / 595.80 / 487.27 / 1 / 599.81 / 495.28 / 20.8
CYP2E1 / EIPFLLEALR / y8 / 2 / 600.85 / 958.57 / 1 / 605.86 / 968.58 / 20.9
CYP2E1 / EIPFLLEALR / y8 / 2 / 600.85 / 479.79 / 2 / 605.86 / 484.79 / 20.9
CYP2E1 / EIPFLLEALR / y6 / 2 / 600.85 / 714.45 / 1 / 605.86 / 724.46 / 20.9
CYP3A12 / LNAQGIIQPEKPIVLK / y14 / 3 / 587.69 / 767.47 / 2 / 590.36 / 771.48 / 24.6
CYP3A12 / LNAQGIIQPEKPIVLK / y12 / 3 / 587.69 / 667.92 / 2 / 590.36 / 671.93 / 24.6
CYP3A12 / LNAQGIIQPEKPIVLK / y8 / 3 / 587.69 / 923.59 / 1 / 590.36 / 931.61 / 24.6
CYP3A12/26 / LQEEIDATFPNK / y10 / 2 / 702.85 / 1163.56 / 1 / 706.86 / 1171.57 / 24 / Shared peptide. Quantitation data not used for protein quantitation.
CYP3A12/26 / LQEEIDATFPNK / y9 / 2 / 702.85 / 1034.52 / 1 / 706.86 / 1042.53 / 24
CYP3A12/26 / LQEEIDATFPNK / y7 / 2 / 702.85 / 792.39 / 1 / 706.86 / 800.40 / 24
CYP3A12/26 / DVEISGVFIPK / y9 / 2 / 602.33 / 989.57 / 1 / 606.34 / 997.58 / 21 / Shared peptide. Quantitation data not used for protein quantitation.
CYP3A12/26 / DVEISGVFIPK / y8 / 2 / 602.33 / 860.52 / 1 / 606.34 / 868.54 / 21
CYP3A12/26 / DVEISGVFIPK / y7 / 2 / 602.33 / 747.44 / 1 / 606.34 / 755.45 / 21
CYP3A26 / GIIQPEKPVVLK / y8 / 3 / 440.95 / 909.58 / 1 / 443.62 / 917.59 / 19
CYP3A26 / GIIQPEKPVVLK / y8 / 3 / 440.95 / 455.29 / 2 / 443.62 / 459.30 / 19
CYP3A26 / GIIQPEKPVVLK / y5 / 3 / 440.95 / 555.39 / 1 / 443.62 / 563.40 / 19

Table 2-S. continued

ProteinName / PeptideSequence / FragmentIon / PrecursorCharge / light PrecursorMz / light ProductMz / ProductCharge / heavy PrecursorMz / heavy ProductMz / CollisionEnergy / Notes
CYP2D15 / GTTLITNLSSVLK / y9 / 2 / 673.90 / 974.59 / 1 / 677.91 / 982.60 / 23.1
CYP2D15 / GTTLITNLSSVLK / y8 / 2 / 673.90 / 861.50 / 1 / 677.91 / 869.52 / 23.1
CYP2D15 / GTTLITNLSSVLK / y7 / 2 / 673.90 / 760.46 / 1 / 677.91 / 768.47 / 23.1
CYP2D15 / VQQEIDEVIGR / y9 / 2 / 643.34 / 1058.55 / 1 / 648.35 / 1068.56 / 22.2
CYP2D15 / VQQEIDEVIGR / y8 / 2 / 643.34 / 930.49 / 1 / 648.35 / 940.50 / 22.2
CYP2D15 / VQQEIDEVIGR / y6 / 2 / 643.34 / 688.36 / 1 / 648.35 / 698.37 / 22.2
CYP2D15 / DTEVQGFLIPK / y7 / 2 / 623.84 / 802.48 / 1 / 627.84 / 810.50 / 21.6
CYP2D15 / DTEVQGFLIPK / y2 / 2 / 623.84 / 244.17 / 1 / 627.84 / 252.18 / 21.6
CYP2D15 / DTEVQGFLIPK / b9 / 2 / 623.84 / 1003.51 / 1 / 627.84 / 1003.51 / 21.6
CYP2C19 / DFIDYFLIK / y7 / 2 / 587.31 / 911.52 / 1 / 591.32 / 919.54 / 20.5
CYP2C19 / DFIDYFLIK / y6 / 2 / 587.31 / 798.44 / 1 / 591.32 / 806.45 / 20.5
CYP2C19 / DFIDYFLIK / y5 / 2 / 587.31 / 683.41 / 1 / 591.32 / 691.43 / 20.5
CYP2C19 / FSLTVLR / y6 / 2 / 418.26 / 688.44 / 1 / 423.26 / 698.44 / 15.5
CYP2C19 / FSLTVLR / y5 / 2 / 418.26 / 601.40 / 1 / 423.26 / 611.41 / 15.5
CYP2C19 / FSLTVLR / y4 / 2 / 418.26 / 488.32 / 1 / 423.26 / 498.33 / 15.5
CYP2C19 / YGLLVLLK / y7 / 2 / 459.80 / 755.54 / 1 / 463.81 / 763.55 / 16.7
CYP2C19 / YGLLVLLK / y6 / 2 / 459.80 / 698.52 / 1 / 463.81 / 706.53 / 16.7
CYP2C19 / YGLLVLLK / y5 / 2 / 459.80 / 585.43 / 1 / 463.81 / 593.45 / 16.7
CYP2B11 / EALVDNAEAFSGR / y10 / 2 / 689.83 / 1065.50 / 1 / 694.84 / 1075.50 / 23.6
CYP2B11 / EALVDNAEAFSGR / y9 / 2 / 689.83 / 966.43 / 1 / 694.84 / 976.44 / 23.6
CYP2B11 / EALVDNAEAFSGR / y8 / 2 / 689.83 / 851.40 / 1 / 694.84 / 861.41 / 23.6
CYP2B11 / QVYNNLQEIK / y8 / 2 / 624.83 / 1021.53 / 1 / 628.84 / 1029.55 / 21.6
CYP2B11 / QVYNNLQEIK / y7 / 2 / 624.83 / 858.47 / 1 / 628.84 / 866.48 / 21.6
CYP2B11 / QVYNNLQEIK / y6 / 2 / 624.83 / 744.43 / 1 / 628.84 / 752.44 / 21.6
CYP2B11 / DFIDAYLIR / y7 / 2 / 563.30 / 863.50 / 1 / 568.30 / 873.51 / 19.8
CYP2B11 / DFIDAYLIR / y6 / 2 / 563.30 / 750.41 / 1 / 568.30 / 760.42 / 19.8
CYP2B11 / DFIDAYLIR / y5 / 2 / 563.30 / 635.39 / 1 / 568.30 / 645.40 / 19.8
CYP2B11 / NLIDTALSLFFAGTETTSTTLR / y10 / 3 / 791.42 / 1066.54 / 1 / 794.75 / 1076.55 / 32.4 / Heavy labelled standard compromised during storage. Quantitation data ignored.
CYP2B11 / NLIDTALSLFFAGTETTSTTLR / y7 / 3 / 791.42 / 779.43 / 1 / 794.75 / 789.43 / 32.4
CYP2B11 / NLIDTALSLFFAGTETTSTTLR / y5 / 3 / 791.42 / 577.33 / 1 / 794.75 / 587.34 / 32.4
UGT1A1 / GVFENVPLLR / y7 / 2 / 572.33 / 840.49 / 1 / 577.33 / 850.50 / 18.1
UGT1A1 / GVFENVPLLR / y6 / 2 / 572.33 / 711.45 / 1 / 577.33 / 721.46 / 19.1
UGT1A1 / GVFENVPLLR / y4 / 2 / 572.33 / 498.34 / 1 / 577.33 / 508.35 / 19.1

Table 2-S. continued

ProteinName / PeptideSequence / FragmentIon / PrecursorCharge / light PrecursorMz / light ProductMz / ProductCharge / heavy PrecursorMz / heavy ProductMz / CollisionEnergy / Notes
UGT1A1 / EDVEATFTSLGR / y8 / 2 / 662.82 / 852.46 / 1 / 667.83 / 862.47 / 22.8
UGT1A1 / EDVEATFTSLGR / y7 / 2 / 662.82 / 781.42 / 1 / 667.83 / 791.43 / 22.8
UGT1A1 / EDVEATFTSLGR / y6 / 2 / 662.82 / 680.37 / 1 / 667.83 / 690.38 / 22.8
UGT1A10 / NFSDSHWNIR / y9 / 3 / 425.87 / 581.28 / 2 / 429.20 / 586.28 / 13.5
UGT1A10 / NFSDSHWNIR / y7 / 3 / 425.87 / 464.23 / 2 / 429.20 / 469.23 / 14.5
UGT1A10 / NFSDSHWNIR / y4 / 3 / 425.87 / 588.33 / 1 / 429.20 / 598.33 / 18.5
UGT1A11 / TYSTTYNLEELNQK / y9 / 2 / 852.41 / 1150.57 / 1 / 856.42 / 1158.59 / 28.5
UGT1A11 / TYSTTYNLEELNQK / y8 / 2 / 852.41 / 987.51 / 1 / 856.42 / 995.52 / 27.5
UGT1A11 / TYSTTYNLEELNQK / y7 / 2 / 852.41 / 873.47 / 1 / 856.42 / 881.48 / 28.5
UGT1A11 / TFSDSQWNIR / y8 / 2 / 627.30 / 1005.47 / 1 / 632.30 / 1015.48 / 21.7
UGT1A11 / TFSDSQWNIR / y6 / 2 / 627.30 / 803.42 / 1 / 632.30 / 813.42 / 21.7
UGT1A11 / TFSDSQWNIR / y5 / 2 / 627.30 / 716.38 / 1 / 632.30 / 726.39 / 22.7
UGT1A2 / TATLIFQR / y6 / 2 / 475.28 / 777.46 / 1 / 480.28 / 787.47 / 15.2
UGT1A2 / TATLIFQR / y5 / 2 / 475.28 / 676.41 / 1 / 480.28 / 686.42 / 16.2
UGT1A2 / TATLIFQR / y4 / 2 / 475.28 / 563.33 / 1 / 480.28 / 573.34 / 16.2
UGT1A2 / EVSLEDILSSGSVWLFR / y10 / 2 / 969.00 / 1151.62 / 1 / 974.01 / 1161.63 / 32 / High unexplained variability in quantitation results and the heavy peptide peak area. Quantitation data ignored.
UGT1A2 / EVSLEDILSSGSVWLFR / y9 / 2 / 969.00 / 1038.54 / 1 / 974.01 / 1048.54 / 32
UGT1A2 / EVSLEDILSSGSVWLFR / y8 / 2 / 969.00 / 951.50 / 1 / 974.01 / 961.51 / 32
UGT1A3 / ILLGQSYLVFER / y9 / 2 / 719.41 / 1098.56 / 1 / 724.41 / 1108.57 / 24.5
UGT1A3 / ILLGQSYLVFER / y7 / 2 / 719.41 / 913.48 / 1 / 724.41 / 923.49 / 24.5
UGT1A3 / ILLGQSYLVFER / y6 / 2 / 719.41 / 826.45 / 1 / 724.41 / 836.45 / 23.5
UGT1A3 / AAALIFQR / y6 / 2 / 445.27 / 747.45 / 1 / 450.27 / 757.46 / 15.3
UGT1A3 / AAALIFQR / y5 / 2 / 445.27 / 676.41 / 1 / 450.27 / 686.42 / 16.3
UGT1A3 / AAALIFQR / y4 / 2 / 445.27 / 563.33 / 1 / 450.27 / 573.34 / 15.3
UGT1A4 / EEDFFTLTTYAPPYTR / y11 / 2 / 975.96 / 1283.66 / 1 / 980.96 / 1293.67 / 29.2
UGT1A4 / EEDFFTLTTYAPPYTR / y10 / 2 / 975.96 / 1182.62 / 1 / 980.96 / 1192.62 / 32.2
UGT1A4 / EEDFFTLTTYAPPYTR / y5 / 2 / 975.96 / 633.34 / 1 / 980.96 / 643.34 / 32.2
UGT1A4 / TVTSFYQR / y6 / 2 / 501.26 / 801.39 / 1 / 506.26 / 811.40 / 17.9
UGT1A4 / TVTSFYQR / y5 / 2 / 501.26 / 700.34 / 1 / 506.26 / 710.35 / 17.9
UGT1A4 / TVTSFYQR / y4 / 2 / 501.26 / 613.31 / 1 / 506.26 / 623.32 / 17.9
UGT1A6 / YEDLASNILK / y8 / 2 / 583.31 / 873.50 / 1 / 587.32 / 881.52 / 19.4
UGT1A6 / YEDLASNILK / y7 / 2 / 583.31 / 758.48 / 1 / 587.32 / 766.49 / 18.4
UGT1A6 / YEDLASNILK / y6 / 2 / 583.31 / 645.39 / 1 / 587.32 / 653.41 / 18.4

Table 2-S. continued

ProteinName / PeptideSequence / FragmentIon / PrecursorCharge / light PrecursorMz / light ProductMz / ProductCharge / heavy PrecursorMz / heavy ProductMz / CollisionEnergy / Notes
UGT1A6 / YEDLASNILK / y8 / 2 / 583.31 / 873.50 / 1 / 587.32 / 881.52 / 19.4
UGT1A6 / YEDLASNILK / y7 / 2 / 583.31 / 758.48 / 1 / 587.32 / 766.49 / 18.4
UGT1A6 / YEDLASNILK / y6 / 2 / 583.31 / 645.39 / 1 / 587.32 / 653.41 / 18.4
UGT1A6 / QIYSVPFGQEELENR / y10 / 2 / 896.43 / 1218.57 / 1 / 901.44 / 1228.58 / 26.8
UGT1A6 / QIYSVPFGQEELENR / y10 / 2 / 896.43 / 609.79 / 2 / 901.44 / 614.80 / 26.8
UGT1A6 / QIYSVPFGQEELENR / y8 / 2 / 896.43 / 974.45 / 1 / 901.44 / 984.46 / 27.8
UGT1A7 / ADFVLDYPK / y7 / 2 / 534.27 / 881.48 / 1 / 538.28 / 889.49 / 15.9
UGT1A7 / ADFVLDYPK / y6 / 2 / 534.27 / 734.41 / 1 / 538.28 / 742.42 / 16.9
UGT1A7 / ADFVLDYPK / y5 / 2 / 534.27 / 635.34 / 1 / 538.28 / 643.35 / 15.9
UGT1A9 / TFSDSHWNIR / y8 / 2 / 631.80 / 1014.48 / 1 / 636.80 / 1024.48 / 23.9
UGT1A9 / TFSDSHWNIR / y6 / 2 / 631.80 / 812.42 / 1 / 636.80 / 822.42 / 23.9
UGT1A9 / TFSDSHWNIR / y5 / 2 / 631.80 / 725.38 / 1 / 636.80 / 735.39 / 23.9
UGT1A9 / DTTLIEYIK / y7 / 2 / 548.30 / 879.52 / 1 / 552.31 / 887.53 / 15.4
UGT1A9 / DTTLIEYIK / y6 / 2 / 548.30 / 778.47 / 1 / 552.31 / 786.49 / 15.4
UGT1A9 / DTTLIEYIK / y5 / 2 / 548.30 / 665.39 / 1 / 552.31 / 673.40 / 16.4
UGT2A1 / NILLLSLK / y6 / 2 / 457.31 / 686.48 / 1 / 461.31 / 694.50 / 15.6
UGT2A1 / NILLLSLK / y5 / 2 / 457.31 / 573.40 / 1 / 461.31 / 581.41 / 15.6
UGT2A1 / NILLLSLK / y4 / 2 / 457.31 / 460.31 / 1 / 461.31 / 468.33 / 16.6
UGT2A1 / IIIDELIK / y6 / 2 / 478.80 / 730.43 / 1 / 482.81 / 738.45 / 15.3
UGT2A1 / IIIDELIK / y5 / 2 / 478.80 / 617.35 / 1 / 482.81 / 625.36 / 16.3
UGT2A1 / IIIDELIK / y4 / 2 / 478.80 / 502.32 / 1 / 482.81 / 510.34 / 16.3
UGT2A2 / INIQICDGVLSNPK / y10 / 2 / 785.92 / 1102.56 / 1 / 789.92 / 1110.57 / 24.5
UGT2A2 / INIQICDGVLSNPK / y9 / 2 / 785.92 / 989.47 / 1 / 789.92 / 997.49 / 25.5
UGT2A2 / INIQICDGVLSNPK / y8 / 2 / 785.92 / 829.44 / 1 / 789.92 / 837.46 / 25.5
UGT2A2 / LLDTFFR / y5 / 2 / 456.25 / 685.33 / 1 / 461.26 / 695.34 / 14.6
UGT2A2 / LLDTFFR / y4 / 2 / 456.25 / 570.30 / 1 / 461.26 / 580.31 / 15.6
UGT2A2 / LLDTFFR / y3 / 2 / 456.25 / 469.26 / 1 / 461.26 / 479.26 / 16.6
UGT2A2 / IILEELIQR / y7 / 2 / 563.85 / 900.51 / 1 / 568.85 / 910.52 / 19.8
UGT2A2 / IILEELIQR / y6 / 2 / 563.85 / 787.43 / 1 / 568.85 / 797.44 / 19.8
UGT2A2 / IILEELIQR / y5 / 2 / 563.85 / 658.39 / 1 / 568.85 / 668.40 / 19.8
UGT2B31 / IPLVYSLR / y7 / 2 / 480.80 / 424.26 / 2 / 485.80 / 429.26 / 17.3
UGT2B31 / IPLVYSLR / y6 / 2 / 480.80 / 750.45 / 1 / 485.80 / 760.46 / 20.3
UGT2B31 / IPLVYSLR / y5 / 2 / 480.80 / 637.37 / 1 / 485.80 / 647.38 / 20.3
UGT2B31 / ANVIASALAQIPQK / y10 / 2 / 712.42 / 1026.59 / 1 / 716.42 / 1034.61 / 23.3
UGT2B31 / ANVIASALAQIPQK / y9 / 2 / 712.42 / 955.56 / 1 / 716.42 / 963.57 / 23.3
UGT2B31 / ANVIASALAQIPQK / y3 / 2 / 712.42 / 372.22 / 1 / 716.42 / 380.24 / 22.3

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