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Supplemental Tables

Table S1: List of MRM transitions monitored.

Q1 Q3 Compound ID DP [V] CE [eV]

315.4 193.3 THC/CBD/CBC-1 90 26

315.5 259.3 THC/CBD/CBC-2 105 28

313.2 193.3 11OH-THC-1 96 39

313.2 133.2 11OH-THC-2 96 35

345.4 299.4 THC-COOH/THC-gluc-1 130 28

345.4 327.5 THC-COOH/THC-gluc-2 130 23

521.5 345.0 THC-gluc-1 101 21

543.6 367.0 THC-gluc-2 101 25

287.3 165.2 THCV/CBDV-1 112 30

287.3 231.2 THCV/CBDV-2 112 25

317.4 271.2 THCV-COOH-1 134 33

317.4 299.1 THCV-COOH-2 134 20

317.5 193.3 CBG-1 69 23

317.5 123.3 CBG-2 69 45

311.3 223.2 CBN-1 138 29

311.3 293.4 CBN-2 138 24

334.4 201.2 11OH-THC-d3 96 39

318.4 196.3 THCd3/CBDd3 102 30

314.5 223.3 CBN-d3 111 28

351.4 305.7 THC-COOH-d6 148 27

Abbreviations: CE: collision energy; CXP: collision cell exit potential; EP: entrance potential; DP: declustering potential; Q: quadrupole;“−1” refers to quantifier transition;

“−2” refers to qualifier transition. Dwell time was 15 ms for all compounds.

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Table S2: Settings used for quantification

Compound Q1/Q3 Expected RT Internal Standard

used Q1/Q3 of IS

11OH-THC 313.2/193.0 3.88 11OH-THC-d3 316.2/196.1

CBN 311.4/223.1 4.52 CBN-d3 314.5/223.1

CBG 317.3/193.1 4.14 CBD-d3 318.4/196.3

THC 315.2/193.1 4.68 THC-d3 318.4/196.3

CBD 315.2/193.1 4.16 CBD-d3 318.4/196.3

CBC 315.2/193.1 4.88 THC-d3 318.4/196.3

THCV 287.1/165.2 4.23 THC-d3 318.4/196.3

CBDV 287.1/165.2 3.72 THC-d3 318.4/196.3

THC-COOH 345.3/299.3 3.98 THC-COOH-d6 351.4/305.7

THCV-COOH 317.4/271.3 3.38 THC-COOH-d6 351.4/305.7

THC-gluc 345.3/299.3 3.39 CBD-d3 318.4/196.3

Abbreviations: IS: internal standard, Q1/Q3: ion transition (m/z=), RT: retention time

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Table S3A: Freeze–thaw and autosampler stability in plasma.

A mixed lot of plasma was evaluated at three concentration levels (n = 3 per concentration level). The freeze–thaw stability values are normalized to values of freshly extracted samples. Samples that have been extracted and stored in the autosampler were compared to two freshly extracted calibration curves for the autosampler stability. Mean accuracies are shown. %CV: coefficient of variance.

Freeze–thaw-1 Freeze–thaw-2 Freeze–thaw-3 48-hour Autosampler Accuracy %CV Accuracy %CV Accuracy %CV Accuracy %CV

11OH-THC 100.5 4.1 97.9 9.4 103.3 22.2 82.3 9.5

CBN 103.2 7.1 88.8 15.9 93.9 5.7 93.5 6.0

CBG 103.2 2.6 92.3 21.5 98.9 3.6 100.5 3.4

THC 102.0 0.1 91.8 19.9 96.0 2.2 101.5 5.1

THCV 98.8 0.7 85.6 24.6 95.6 5.1 94.9 1.5

THC-COOH 104.1 1.4 92.6 21.7 101.0 7.3 99.8 5.4

THCV-COOH 96.6 8.2 88.4 13.3 100.0 18.2 86.6 5.6

CBD 103.0 2.8 90.5 21.9 96.8 2.9 100.8 3.7

CBC 101.7 2.3 92.1 16.7 95.1 4.3 107.2 8.9

CBDV 97.6 1.2 86.8 24.0 94.1 6.0 90.4 4.0

THC-gluc 97.8 1.3 88.0 14.4 93.9 7.2 119.6 6.6

Table S3B: Freeze–thaw and autosampler stability in urine.

A mixed lot of urine was evaluated at three concentration levels (n = 3 per concentration level). The freeze–thaw stability values are normalized to values of freshly extracted samples. Samples that have been extracted and stored in the autosampler were compared to two freshly extracted calibration curves for the autosampler stability. Mean accuracies are shown. %CV: coefficient of variance.

Freeze–thaw-1 Freeze–thaw-2 Freeze–thaw-3 48-hour Autosampler Accuracy %CV Accuracy %CV Accuracy %CV Accuracy %CV

11OH-THC 92.8 4.2 101.1 19.4 108.6 6.2 108.6 5.7

CBN 95.3 10.5 90.6 7.7 95.9 4.7 109.6 2.6

CBG 89.1 2.7 82.4 4.9 95.0 3.8 101.2 5.2

THC 96.7 5.3 88.5 5.3 97.3 7.5 106.7 3.2

THCV 99.0 3.3 93.6 11.9 95.3 1.4 108.7 1.1

THC-COOH 98.2 4.9 92.2 13.1 98.0 3.1 102.9 5.4

THCV-COOH 92.2 5.8 92.8 14.2 101.3 0.8 105.8 7.8

CBD 93.8 2.7 91.4 7.0 94.7 5.2 107.3 0.8

CBC 94.4 1.0 85.5 3.3 95.4 3.9 108.0 2.8

CBDV 101.8 6.3 97.5 12.6 99.0 3.9 112.3 4.5

THC-gluc 101.7 4.2 94.2 8.6 97.4 5.8 103.7 3.3

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Table S4A: Short-term stability in plasma.

A mixed lot of plasma was evaluated at three concentration levels (n = 3 per concentration level).

Abbreviations: BT, benchtop. Mean % of the corresponding concentration levels of freshly extracted and analyzed sample sets are shown.

2 hours 4 hours 24 hours 1 week

BT 4 °C BT 4 °C BT 4 °C 4 °C −20 °C −80 °C 11OH-THC 109.4 98.4 115.4 107.7 109.2 96.8 109.0 91.8 95.1

CBN 103.3 100.4 105.8 104.9 102.2 102.7 99.9 95.9 98.4

CBG 101.4 96.2 103.0 102.7 99.1 101.1 102.4 96.0 99.8

THC 103.1 100.3 103.2 105.1 101.4 101.8 106.0 101.8 103.5 THCV 104.8 99.8 105.2 105.2 97.2 100.3 106.7 105.6 105.3 THC-COOH 104.5 104.1 102.5 106.3 104.8 107.2 103.7 97.6 100.0 THCV-COOH 103.8 101.7 99.3 103.7 98.4 103.8 103.3 102.2 99.8

CBD 102.8 102.0 106.7 106.4 103.2 105.2 106.5 102.8 105.5 CBC 105.0 104.1 106.7 107.9 101.5 102.8 106.2 101.8 104.7 CBDV 103.4 101.2 101.9 103.8 97.4 101.5 108.1 105.9 102.0 THC-gluc 104.2 102.0 101.3 100.9 92.5 100.2 102.4 98.1 101.9

Table S4B: Short-term stability in urine.

A mixed lot of urine was evaluated at three concentration levels (n = 3 per level) (n = 3 per concentration level). Abbreviations: BT, benchtop. Mean % of the corresponding concentration levels of freshly extracted and analyzed sample sets are shown.

2 hours 4 hours 24 hours 1 week

BT 4 °C BT 4 °C BT 4 °C 4 °C −20 °C −80 °C 11OH-THC 101.0 90.2 100.6 89.8 91.4 93.9 90.2 101.7 108.5

CBN 96.1 97.7 100.8 90.9 89.3 93.3 91.9 97.4 99.9

CBG 92.9 93.9 98.1 87.7 87.1 92.7 98.2 98.1 99.6

THC 93.2 94.3 100.0 90.3 92.5 97.4 103.6 102.4 106.4

THCV 99.6 100.1 105.5 96.9 102.6 99.1 105.0 104.7 108.5

THC-COOH 102.9 97.4 106.5 97.0 113.4 99.5 100.6 98.7 102.6 THCV-COOH 96.2 96.0 99.8 97.6 99.9 95.7 102.5 99.5 104.7

CBD 100.1 98.6 102.1 94.2 96.8 98.3 105.6 103.5 106.6

CBC 87.5 93.5 95.5 85.7 79.4 91.1 102.7 100.4 104.9

CBDV 103.0 101.0 105.8 98.9 106.9 104.1 107.0 104.7 109.3 THC-gluc 103.5 101.6 104.5 101.0 103.6 101.2 91.7 97.9 100.5

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Table S5: Long-term stability in urine and plasma.

A mixed lot of urine was evaluated at three concentration levels (n = 3 per concentration level).

Abbreviations: BT, benchtop. Mean % of the corresponding concentration levels of freshly extracted and analyzed sample sets are shown.

Plasma Urine

1 month 4 month 1 month 4 month

−20 °C −80 °C −20 °C −80 °C −20 °C −80 °C −20 °C −80 °C

11OH-THC 80.8 78.5 88.0 87.3 87.6 78.8 86.0 86.7

CBN 87.4 99.8 73.7 70.6 89.3 83.9 83.4 85.5

CBG 71.7 79.0 72.7 74.1 101.9 93.0 74.7 80.3

THC 76.7 80.1 70.6 69.8 102.9 92.9 98.8 102.7

THCV 87.6 94.5 81.8 85.6 105.5 98.2 106.5 111.5

THC-COOH 79.6 83.8 70.7 73.2 96.4 88.0 91.7 98.0

THCV-COOH 76.4 80.9 68.3 69.6 102.2 99.2 102.2 109.1

CBD 72.8 77.0 75.3 73.0 112.6 103.8 98.5 104.2

CBC 71.5 85.5 70.2 68.0 111.9 101.7 86.8 84.4

CBDV 86.5 91.8 90.0 91.3 113.8 105.9 110.5 111.8

THC-gluc 96.3 105.4 89.5 93.6 101.0 96.3 107.8 116.1

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