Table 1.
Veliparib concentrations by LC-MS (left) and its spatial distribution by MALDI (bottom) varies by tissue, drug dose and TNBC cell line of origin
| Tissue | Amount of tissue median (RSE) |
Comparison | Method | Subjects (N) | Tissues (N) | Tissues (N) <LOD; <LOQ |
Median conc. (RSE %)a |
Ion intensity tumor/muscle (RSE %); |
P | ||
|---|---|---|---|---|---|---|---|---|---|---|---|
| a) Veliparib | Plasma | 50 μL | 20 mg/kg 60 mg/kg |
LC-MS | 9 6 |
9 6 |
1; 0 0; 0 |
0.19 (10) 0.86 (11) |
<0.001 (Low/high dose) | ||
| Muscle | 49.9 mg (13%) | 20 mg/kg 60mg/kg |
5 6 |
5 6 |
2; 3 1; 1 |
0.12 (70) 0.47 (47) |
0.882 (Muscle/plasma)* | ||||
| Liver | 49.9 mg (12%) | 20 mg/kg 60 mg/kg |
6 6 |
6 6 |
0; 0 0; 0 |
0.47 (20) 1.77 (14) |
<0.001 (Liver/plasma)* | ||||
| TNBC xenograft tissue | 46.1 mg (8%) | 20 mg/kg 60 mg/kg |
12 12 |
19 17 |
8; 15 0; 1 |
0.12 (31) 0.36 (12) |
0.322 (Tumor/plasma) 0.0038 (tumor/plasma) |
||||
| HCC70 | 20 mg/kg | 4 | 6 | 2; 4 | 0.13 (43) | 0.0367 (Cell source)* | |||||
| 60 mg/kg | 5 | 9 | 0; 0 | 0.43 (16) | |||||||
| MDA-MB-231 | 20 mg/kg | 4 | 7 | 4; 6 | 0.01 (62) | ||||||
| 60 mg/kg | 4 | 5 | 0; 1 | 0.27 (18) | |||||||
| MDA-MB-436 | 20 mg/kg | 4 | 6 | 2; 5 | 0.05 (47) | ||||||
| 60 mg/kg | 3 | 3 | 0; 0 | 0.32 (26) | |||||||
| 12 μm section | 20 mg/kg 60 mg/kg |
MALDI | 6 9 |
6 12 |
0.98 (16); 0.02 1.36 (19); 0.13 |
<0.001 (Low/high dose) | |||||
| Necrotic tumors Cellular tumors |
15 15 |
18 18 |
1.63 (70%)
1.01 (85%) |
0.084 (ROI)* | |||||||
MALDI matrix-assisted laser desorption/ionization, TBNC triple negative breast cancer, PBMC peripheral blood mononuclear cells, RSE relative standard errors, ROI region of interest, V veliparib
aConcentration (Conc.) of veliparib and carboplatin in mg/L, carboplatin adducts in μmol/g DNA
*P value adjusted for dose