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Clinical Research use only, Not for use Diagnostics Procedure Quantitative analysis of Testosterone in plasma using Q Exactive Kevin He and Marta Kozak Clinical Research Applications Group Thermo Fisher Scientific San Jose, CA

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Page 1: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

Clinical Research use only, Not for use Diagnostics Procedure

Quantitative analysis of Testosterone in

plasma using Q Exactive

Kevin He and Marta Kozak

Clinical Research Applications Group

Thermo Fisher Scientific San Jose, CA

Page 2: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

2 Clinical Research use only, Not for use Diagnostics Procedure

Instrumentation

• LC system: Accela 600 pump

• Q Exactive equipped with APCI + Ion Max TM source

Page 3: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

3 Clinical Research use only, Not for use Diagnostics Procedure

Calibration Curve Standards Preparation

• Calibration standards were prepared in house in charcoal stripped serum (8-14) and in water (1-7).

SampleTestosterone

(pg/mL)

Testosterone-d3

(pg/mL)

Testo On

Column

(pg)

1 0 100 0

2 10 100 1

3 20 100 2

4 50 100 5

5 100 100 10

6 250 100 25

7 500 100 50

8 0 100 0

9 10 100 1

10 20 100 2

11 50 100 5

12 100 100 10

13 250 100 25

14 500 100 50

1-7: water 8-14: CSS

Page 4: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

4 Clinical Research use only, Not for use Diagnostics Procedure

Modified Sample Preparation Procedure

• Place 200 uL of plasma sample into 16x100 mm borosilicate glass tubes

• To 200 uL plasma add 10 uL of 2 ng/mL working I.S. in 50:50 MeOH:Di water, and 10 uL testosterone

(various concentrations in MeOH/MeCN)

• Vortex briefly

• Add 1 mL of MTBE

• Cover with aluminum foil

• Vortex-mix for 90 sec

• Let stand for 5 min at room temperature

• Centrifuge at 4200 rpm for 5 min

• Place tubes in the -30 deg C freezer for 30 min

• Pour the upper layer into the 2nd labeled 16x100 mm glass tube – make sure that the maximum volume is

recovered

• Dry down the tubes in the Turbo-vap for 20 min at 37 deg C

• Reconstitute with 100 uL of 50:50 MeOH:DI water

• Vortex for 60 sec

• Injection volume: 50 µL

Page 5: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

5 Clinical Research use only, Not for use Diagnostics Procedure

LC Method

• Analytical Column: Hypersil GOLD aQ 100 x 2.1 mm, 5µm

• Mobile Phase

� A: 5% MeOH in DI water

� B: MeOH

� C: ACN/IPA/Acetone: 45/45/10

• Autosampler wash solution #1: Water

• Autosampler wash solution #2: MeOH

• LC Gradient

Time(min) %A %B %C Flow (µµµµL/min)

0 95 5 0 400

0.1 60 40 0 400

0.5 60 40 0 400

3.5 5 95 0 400

4.5 5 95 0 400

4.51 0 0 100 600

5 0 0 100 600

5.1 95 5 0 600

6.5 95 5 0 600

Page 6: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

6 Clinical Research use only, Not for use Diagnostics Procedure

Autosampler method

Page 7: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

7 Clinical Research use only, Not for use Diagnostics Procedure

MS Method: source parameters

Q Exactive systemIonization APCI, positive, Ion Max™ source

Vaporizer temperature (deg C) 350

Capillary temperature (deg C) 320

Discharge current (µA) 5.0

Sheath gas (units) 10

Aux gas (units) 20

Probe position C

Divert valve: initial position to waste, at 3 min position to detector and at 5 min position switched back to waste

Page 8: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

8 Clinical Research use only, Not for use Diagnostics Procedure

MS acquisition method

• Acquisition mode: HCD fragmentation with collision energy set to 40 eV

• Precursor isolation width: 2 mu

• Resolution: 70K @ 200 m/z

• AGC Target: 1e5

• Max injection time: 100ms

Page 9: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

9 Clinical Research use only, Not for use Diagnostics Procedure

Acquisition method parameters: screen capture

Page 10: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

10 Clinical Research use only, Not for use Diagnostics Procedure

Testosterone processing parameters (97 m/z ion)

97 m/z ion

from 289.2 m/z

parent ion.

97 m/z ion

from 289.2 m/z

parent ion.

Mass window:

3 ppm

Mass window:

3 ppm

Page 11: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

11 Clinical Research use only, Not for use Diagnostics Procedure

Testosterone processing parameters (109 m/z ion)

109 m/z ion

from 289.2 m/z

parent ion.

109 m/z ion

from 289.2 m/z

parent ion.

Page 12: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

12 Clinical Research use only, Not for use Diagnostics Procedure

Testosterone processing parameters (both ions)

Both ions from

289.2 m/z

parent ion.

Both ions from

289.2 m/z

parent ion.

Ion ratio applied.Ion ratio applied.

Page 13: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

13 Clinical Research use only, Not for use Diagnostics Procedure

Testosterone-d3 processing parameters (both ions)

Both ions from

292.2 m/z

parent ion.

Both ions from

292.2 m/z

parent ion.

Ion ratio applied.Ion ratio applied.

Page 14: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

14 Clinical Research use only, Not for use Diagnostics Procedure

Testo-97Y = 0.0404358+0.00884573*X R^2 = 0.9933 W: 1/X

0 50 100 150 200 250 300 350 400 450 500 550

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

Are

a R

atio

Calibration curve in CSS (97 m/z ion)

Standard % Difference

10 pg/mL 8.76

20 pg/mL 2.63

50 pg/mL -8.94

100 pg/mL 2.89

250 pg/mL -10.76

500 pg/mL 5.41

Page 15: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

15 Clinical Research use only, Not for use Diagnostics Procedure

Testo-109Y = 0.0970157+0.00839124*X R^2 = 0.9980 W: 1/X

0 50 100 150 200 250 300 350 400 450 500 550

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

2.2

2.4

2.6

2.8

3.0

3.2

3.4

3.6

3.8

4.0

4.2

4.4

4.6

4.8

Are

a R

atio

Calibration curve in CSS (109 m/z ion)

Standard % Difference

10 pg/mL 0.97

20 pg/mL 7.45

50 pg/mL -5.78

100 pg/mL -0.29

250 pg/mL -5.35

500 pg/mL 2.99

Page 16: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

16 Clinical Research use only, Not for use Diagnostics Procedure

TestoY = 0.0568976+0.0087523*X R^2 = 0.9935 W: 1/X

0 50 100 150 200 250 300 350 400 450 500 550

0.0

0.5

1.0

1.5

2.0

2.5

3.0

3.5

4.0

4.5

5.0

Are

a R

atio

Calibration curve in CSS (both ions)

Standard % Difference

10 pg/mL 11.27

20 pg/mL -5.50

50 pg/mL -3.41

100 pg/mL 3.57

250 pg/mL -11.09

500 pg/mL 5.17

Page 17: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

17 Clinical Research use only, Not for use Diagnostics Procedure

97 m/z fragment ion (CSS, left: Testo; right: Testo-d3)

RT: 3.70 - 4.50 SM: 5B

3.8 4.0 4.2 4.4

Time (min)

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

RT: 4.15AA: 855806SN: 861

RT: 4.12AA: 392960SN: 451

RT: 4.05AA: 156654SN: 281

RT: 4.05AA: 82432SN: 148

RT: 4.06AA: 32309SN: 85

RT: 4.10AA: 21209SN: 74

RT: 4.13AA: 5093SN: 29

NL: 1.25E5

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 14

NL: 5.21E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 13

NL: 2.54E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 12

NL: 1.26E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 11

NL: 5.98E3

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 10

NL: 4.41E3

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 09

NL: 1.19E3

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 08

RT: 3.70 - 4.50 SM: 5B

3.8 4.0 4.2 4.4

Time (min)

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

RT: 4.14AA: 177542SN: 196

RT: 4.11AA: 189995SN: 166

RT: 4.04AA: 162983SN: 165

RT: 4.04AA: 163899SN: 183

RT: 4.05AA: 150270SN: 176

RT: 4.11AA: 164334SN: 251

RT: 4.11AA: 150535SN: 243

NL: 2.65E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 14

NL: 2.43E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 13

NL: 2.61E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 12

NL: 2.55E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 11

NL: 2.67E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 10

NL: 2.66E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 09

NL: 2.38E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 08

10 pg/mL

20 pg/mL

50 pg/mL

100 pg/mL

250 pg/mL

500 pg/mL

100 pg/mL100 pg/mL

Page 18: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

18 Clinical Research use only, Not for use Diagnostics Procedure

RT: 3.70 - 4.50 SM: 5B

3.8 4.0 4.2 4.4

Time (min)

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

RT: 4.15AA: 784312SN: 1054

RT: 4.12AA: 381337SN: 352

RT: 4.05AA: 149668SN: 251

RT: 4.05AA: 75236SN: 124

RT: 4.06AA: 38873SN: 50

RT: 4.12AA: 20337SN: 33

RT: 4.13AA: 6971SN: 21

NL: 1.11E5

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 14

NL: 4.73E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 13

NL: 2.34E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 12

NL: 1.15E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 11

NL: 5.11E3

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 10

NL: 3.35E3

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 09

NL: 1.50E3

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 08

RT: 3.70 - 4.50 SM: 5B

3.8 4.0 4.2 4.4

Time (min)

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

RT: 4.14AA: 167514SN: 164

4.353.80 3.95

RT: 4.11AA: 175646SN: 132

4.273.883.78 4.38

RT: 4.04AA: 146377SN: 150

RT: 4.04AA: 163055SN: 195

3.75 4.374.253.88

RT: 4.05AA: 146661SN: 178

RT: 4.11AA: 181988SN: 157

3.98 4.32 4.383.80

RT: 4.11AA: 129563SN: 139

4.27 4.453.983.77

NL: 2.37E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 14

NL: 2.03E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 13

NL: 2.27E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 12

NL: 2.44E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 11

NL: 2.52E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 10

NL: 2.39E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 09

NL: 2.16E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 08

109 m/z fragment ion (CSS, left: Testo; right: Testo-d3)

10 pg/mL

20 pg/mL

50 pg/mL

100 pg/mL

250 pg/mL

500 pg/mL

100 pg/mL100 pg/mL

Page 19: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

19 Clinical Research use only, Not for use Diagnostics Procedure

Testo-97Y = 0.0268377+0.00888146*X R^2 = 0.9991 W: 1/X

0 50 100 150 200 250 300 350 400 450 500 550

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

2.2

2.4

2.6

2.8

3.0

3.2

3.4

3.6

3.8

4.0

4.2

4.4

4.6

4.8

Are

a R

atio

Calibration curve in H2O (97 m/z ion)

Standard % Difference

10 pg/mL -0.98

20 pg/mL 3.29

50 pg/mL -6.12

100 pg/mL 2.05

250 pg/mL 3.36

500 pg/mL -1.59

Page 20: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

20 Clinical Research use only, Not for use Diagnostics Procedure

Testo-109Y = 0.036356+0.00864486*X R^2 = 0.9982 W: 1/X

0 50 100 150 200 250 300 350 400 450 500 550

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

2.2

2.4

2.6

2.8

3.0

3.2

3.4

3.6

3.8

4.0

4.2

4.4

4.6

Are

a R

atio

Standard % Difference

10 pg/mL 6.72

20 pg/mL -8.61

50 pg/mL -6.72

100 pg/mL 9.02

250 pg/mL 1.02

500 pg/mL -1.43

Calibration curve in H2O (109 m/z ion)

Page 21: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

21 Clinical Research use only, Not for use Diagnostics Procedure

TestoY = 0.0300348+0.00876047*X R^2 = 0.9995 W: 1/X

0 50 100 150 200 250 300 350 400 450 500 550

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

2.0

2.2

2.4

2.6

2.8

3.0

3.2

3.4

3.6

3.8

4.0

4.2

4.4

4.6

4.8

Are

a R

atio

Calibration curve in H2O (both ions)

Standard % Difference

10 pg/mL NA

20 pg/mL -2.27

50 pg/mL -2.30

100 pg/mL 5.04

250 pg/mL 0.43

500 pg/mL -0.90

Page 22: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

22 Clinical Research use only, Not for use Diagnostics Procedure

97 m/z fragment ion (H2O, left: Testo; right: Testo-d3)

10 pg/mL

20 pg/mL

50 pg/mL

100 pg/mL

250 pg/mL

500 pg/mL

100 pg/mL100 pg/mL

RT: 3.70 - 4.50 SM: 5B

3.8 4.0 4.2 4.4

Time (min)

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

RT: 4.15AA: 731519SN: 1262

RT: 4.23AA: 338779SN: 419

RT: 4.13AA: 127859SN: 218

RT: 4.20AA: 68755SN: 114

RT: 4.12AA: 31493SN: 41

RT: 4.13AA: 18119SN: 173

RT: 4.16AA: 4012SN: 60

NL: 1.17E5

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 07

NL: 5.56E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 06

NL: 1.96E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 05

NL: 1.06E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 04

NL: 5.37E3

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 03

NL: 3.29E3

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 02

NL: 9.40E2

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 01

RT: 3.70 - 4.50 SM: 5B

3.8 4.0 4.2 4.4

Time (min)

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

RT: 4.14AA: 174109SN: 580

RT: 4.22AA: 154715SN: 390

RT: 4.12AA: 151383SN: 298

RT: 4.20AA: 153346SN: 317

RT: 4.11AA: 167461SN: 387

RT: 4.12AA: 152585SN: 407

RT: 4.15AA: 143067SN: 234

NL: 2.87E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 07

NL: 2.44E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 06

NL: 2.29E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 05

NL: 2.52E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 04

NL: 2.61E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 03

NL: 2.65E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 02

NL: 2.24E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 01

Page 23: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

23 Clinical Research use only, Not for use Diagnostics Procedure

109 m/z fragment ion (H2O, left: Testo; right: Testo-d3)

10 pg/mL

20 pg/mL

50 pg/mL

100 pg/mL

250 pg/mL

500 pg/mL

100 pg/mL100 pg/mL

RT: 3.70 - 4.50 SM: 5B

3.8 4.0 4.2 4.4

Time (min)

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

RT: 4.15AA: 668828SN: 1146

RT: 4.22AA: 309183SN: 851

RT: 4.13AA: 121461SN: 229

RT: 4.20AA: 61020SN: 192

RT: 4.10AA: 26842SN: 166

4.29 4.44

RT: 4.13AA: 18598SN: 222

4.243.96 4.44

RT: 4.16AA: 5012SN: 31

NL: 1.06E5

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 07

NL: 4.81E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 06

NL: 1.77E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 05

NL: 1.04E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 04

NL: 4.57E3

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 03

NL: 3.79E3

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 02

NL: 9.85E2

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 01

RT: 3.70 - 4.50 SM: 5B

3.8 4.0 4.2 4.4

Time (min)

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

0

50

100

RT: 4.14AA: 157317SN: 316

RT: 4.22AA: 136573SN: 265

4.393.983.77 3.92

RT: 4.12AA: 141279SN: 294

RT: 4.20AA: 149539SN: 286

RT: 4.11AA: 149154SN: 489

4.34 4.473.78 3.83

RT: 4.12AA: 130006SN: 366

4.34 4.473.78 3.87

RT: 4.15AA: 138849SN: 208

NL: 2.49E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 07

NL: 2.21E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 06

NL: 2.08E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 05

NL: 2.31E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 04

NL: 2.38E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 03

NL: 2.23E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 02

NL: 2.15E4

m/z= 109.0643-109.0653 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 01

Page 24: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

24 Clinical Research use only, Not for use Diagnostics Procedure

20 pg/mL Testosterone (and I.S. 100 pg/mL) in CSS

RT: 3.93 - 4.25

3.95 4.00 4.05 4.10 4.15 4.20 4.25

Time (min)

0

20

40

60

80

100

Re

lative

Ab

un

da

nce

0

20

40

60

80

100

Re

lative

Ab

un

da

nce

0

20

40

60

80

100

Re

lative

Ab

un

da

nce

0

20

40

60

80

100

Re

lative

Ab

un

da

nce

RT: 4.07AA: 32298SN: 33

RT: 4.05AA: 155314SN: 169

RT: 4.07AA: 40108SN: 40

RT: 4.05AA: 147559SN: 165

NL: 7.43E3

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 10

NL: 3.08E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 10

NL: 6.38E3

m/z= 109.0647-109.0657 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 10

NL: 3.21E4

m/z= 109.0647-109.0657 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS 10

10 #572 RT: 4.07 AV: 1 NL: 2.98E4F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00]

95 100 105 110

m/z

0

5

10

15

20

25

30

35

40

45

50

55

60

65

70

75

80

85

90

95

100

Re

lative

Ab

un

da

nce

97.0654R=108800

109.0652R=103900

107.0859R=9030095.0861

R=99500 105.0703R=7860098.1048

R=64000100.2727R=62200

Testo

Testo

Testo-d3

Testo-d3

97 m/z ion97 m/z ion

109 m/z ion109 m/z ion

15 scans in 6 sec, at 100K resolution for fragments

Page 25: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

25 Clinical Research use only, Not for use Diagnostics Procedure

RT: 3.00 - 5.00 SM: 5B

3.0 3.5 4.0 4.5 5.0

Time (min)

0

10

20

30

40

50

60

70

80

90

100

Re

lative

Ab

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0

10

20

30

40

50

60

70

80

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Re

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Ab

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nce

RT: 4.17AA: 347921SN: 310

3.96

4.73 4.944.403.703.31 3.36

RT: 4.18AA: 216369SN: 209

4.984.694.39

3.30 3.53 3.67 3.943.06

NL: 6.32E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS T2

NL: 3.72E4

m/z= 97.0649-97.0659 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS T2

RT: 3.00 - 5.00 SM: 5B

3.0 3.5 4.0 4.5 5.0

Time (min)

0

10

20

30

40

50

60

70

80

90

100

Re

lative

Ab

un

da

nce

0

10

20

30

40

50

60

70

80

90

100

Re

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Ab

un

da

nce

RT: 4.17AA: 311283SN: 380RMS

3.96

4.934.633.723.363.08

RT: 4.17AA: 196492SN: 275RMS

4.76

4.68

4.51

3.07 3.983.823.13 3.73

NL: 5.45E4

m/z= 109.0647-109.0657 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS T2

NL: 3.58E4

m/z= 109.0647-109.0657 F: FTMS + p APCI corona Full ms2 [email protected] [50.00-315.00] MS ICIS T2

Clinical Plasma sample T2 (left: 97 m/z; right: 109 m/z)

Testo-d3 Testo-d3

Testo Testo

Page 26: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

26 Clinical Research use only, Not for use Diagnostics Procedure

In CSS

97.0654 m/z R20.9933 Slope 8.85E-03

in CSS Conc. (pg/mL) % Dif Patient Conc. (ng/dL)

Cal1 10 8.76 T1 15

Cal2 20 2.63 T2 17

Cal3 50 -8.94 T3 156

Cal4 100 2.89 T4 34

Cal5 250 -10.76 T5 8

Cal6 500 5.41

109.0652 m/z R20.998 Slope 8.39E-03

Cal1 10 0.97 T1 13

Cal2 20 7.45 T2 19

Cal3 50 -5.78 T3 156

Cal4 100 -0.29 T4 37

Cal5 250 -5.35 T5 8

Cal6 500 2.99

Both ions R20.9935 Slope 8.75E-03

Cal1 10 11.27 T1 15

Cal2 20 -5.5 T2 17

Cal3 50 -3.41 T3 164

Cal4 100 3.57 T4 36

Cal5 250 -11.09 T5 9

Cal6 500 5.17

Page 27: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

27 Clinical Research use only, Not for use Diagnostics Procedure

97.0654 m/z R20.9991 Slope 8.88E-03

in H2O Conc. (pg/mL) % Dif Patient Conc. (ng/dL)

Cal1 10 -0.98 T1 15

Cal2 20 3.29 T2 17

Cal3 50 -6.12 T3 156

Cal4 100 2.05 T4 34

Cal5 250 3.36 T5 8

Cal6 500 -1.59

109.0652 m/z R20.9982 Slope 8.64E-03

Cal1 10 6.72 T1 14

Cal2 20 -8.61 T2 20

Cal3 50 -6.72 T3 152

Cal4 100 9.02 T4 36

Cal5 250 1.02 T5 7

Cal6 500 -1.43

Both ions R20.9995 Slope 8.76E-03

Cal1 10 NA T1 15

Cal2 20 -2.27 T2 18

Cal3 50 -2.3 T3 164

Cal4 100 5.04 T4 36

Cal5 250 0.43 T5 9

Cal6 500 -0.9

In water

Page 28: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

28 Clinical Research use only, Not for use Diagnostics Procedure

Donor samples data vs immunoassay results

Sample Fragment 97 Fragment 109 Immunoassay results

ng/dL Calibrators in

water

Calibrators in plasma Calibrators in

water

Calibrators in

plasma

T1 15 15 13 14 21 ng/dl

T2 17 17 19 20 38 ng/dL

T3 156 156 156 152 178 ng/dL

T3 34 34 37 36 62 ng/dL

T5 8 8 8 7 <20 ng/dL

Page 29: Testosterone using Q Exactive - Orbitrap • Centrifuge at 4200 rpm for 5 min • Place tubes in the -30 deg C freezer for 30 min • Pour the upper layer into the 2 nd labeled 16x100

29 Clinical Research use only, Not for use Diagnostics Procedure

Conclusion

• Q Exactive LC-MS/MS system has high sensitivity and specificity needed for

Testosterone analysis in plasma matrix