8
Table 6: MRM parameters for anticonvulsants Name
Carbamazepine
Carbamazepine-10,11- Epoxide
Gabapentin Lamotrigine Levetiracetam Pregabalin Zonisamide
13C6-Zonisamide Lacosamide
D5-Phenobarbital Phenobarbital Phenytoin Topiramate Valproic Acid Clonazepam Diazepam
N-Desmethylclobazam Nitrazepam Nordiazepam Clobazam
pos pos
pos pos pos pos pos pos pos neg neg neg neg neg pos pos pos pos pos pos
Table 8: Anticonvulsant QC Results
Ionisation Quantification MRM CE(V)
237 > 192 -21 253 > 210 -12
172 > 154 -15 256 > 211 -26 171 > 126 -15 160 > 55 -22 213 > 132 -14 219 > 138 -15 251 > 108 -20 236 > 42 24 231 > 42 22 251 > 102 23 338 > 78 31 143 > 143 11 316 > 214 -38 285 > 193 -31 287 > 245 -18 282 > 236 -24 271 > 140 -27 301 > 259 -21
Table 7: Recovery results for anticonvulsants CBZ
Total Recovery (%)
EPO- CBZ
QC LOQ QC A QC B QC C
Mean %RSD
Pool A Pool B Pool A Pool B Pool A Pool B Pool A Pool B
101 108 98.7 101 114 113 104 97.6 105
103 109 103 104 110 112 105 99.6 106
GBP LMT
92.0 97.3 91.9 91.8 102 98.9 94.3 87.2 94.4
84.2 92.2 83.9 85.9 94.9 94.6 91.7 86.4 89.2
LVT
109 119 107 109 118 120 110 106 112
PGB ZNA LCA
89.4 96.4 90.0 90.9 102 99.9 95.5 88.4 94.1
82.6 91.3 82.2 84.8 94.1 93.1 88.8 82.2 87.4
86.9 95.4 88.1 90.4 99.6 98.9 94.5 88.7 92.8
PBR
81.8 90.9 83.0 77.5 90.7 88.6 85.0 78.8 84.5
6% 4% 5% 5% 5% 5% 6% 5% 6% PNT QC LOQ QC A QC B QC C
Mean %RSD
Pool A Pool B Pool A Pool B Pool A Pool B Pool A Pool B
78.0 85.8 82.1 80.0 89.6 89.2 83.8 77.2 83.2
TPA VPA
75.9 86.8 77.5 79.4 88.1 86.9 79.3 73.7 81.0
(*) Excluded values due to plasma contamination. 6. Conclusion
LC-MS/MS has unique advantages and capabilities which make this technique a key technology asset in TDM laboratories. Advances in hardware engineering and software design are making a high impact for laboratories without the need for highly trained operators and this development is likely to continue to further automate assays and to expand the number of drugs measured by TDM. In this brief review, automated solutions for immunosuppressants and anticonvulsants have highlighted the considerable advance in integrated system designs for routine clinical pathology laboratories using LC-MS/MS.
81.1 87.3 83.1 85.0 93.6 91.7 88.0 80.4 86.3
CZP
105 125 83.8 94.9 92.3 89.1 89.2 84.3 91.2
DIA DM- CLBZ
80.3 96.1 77.1 82.4 88.0 89.0 86.0 79.1 84.8
77.3 84.2 83.2 88.1 95.5 93.7 90.2 83.2 86.9
NTZ NDIA CLBZ 82.7 84.2
93.9 121* 85.0 86.0 92.9 91.3 89.2 82.5 87.9
85.4 94.0 93.0 97.2 90.1 84.4 89.8
84.4 93.5 84.0 84.9 95.0 94.1 89.0 81.5 88.3
6% 7% 6% 8% 7% 7% 5% 6% 6% References
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Confirmation MRM CE(V)
237 > 165 -43 253 > 167 -35
172 > 137 -16 256 > 43 -53 171 > 69 -27 160 > 97 -14 213 > 77 -33 ---
---
251 > 91 -50 ---
---
231 > 188 11 251 > 208 16 338 > 96 25 ---
---
316 > 270 -25 285 > 154 -27 287 > 210 -31 282 > 180 -38 271 > 165 -27 301 > 224 -32
Dwell
Time (ms) 8 8
19 14 19 24 12 26 12 18 8 8 8
20 8 9 8 8 9 8
QC LOQ QC A Mean Accuracy
%RSD 2% 2% 0.8% 0.5% 3% 3% 0.7% 1% 8% Mean
Accuracy QC B
%RSD 3% 3% 0.5% 0.8% 3% 0.5% 0.3% 1% 5% Mean
Accuracy QC C
%RSD 3% 2% 0.2% 0.9% 2% 1% 0.8% 1% 3% Mean
Accuracy
%RSD 3% 4% 0.3% 1% 3% 0.3% 0.6% 1% 1% PNT
TPA VPA QC LOQ QC A Mean Accuracy
%RSD 12% 3% 3% 16% 2% 4% 6% 3% 2% Mean
Accuracy QC B
%RSD 4% 2% 2% 11% 0.6% 2% 2% 1% 2% Mean
Accuracy QC C
%RSD 3% 2% 1% 7% 0.7% 1% 1% 0.7% 0.7% Mean
98.6 99.7 100 102 104 103 104 102 107 Accuracy %RSD 3% 2% 2% 3% 2% 1% 0.5% 2% 2% 100 96.1 98.0 95.7 93.4 97.6 98.3 92.0 97.7 104 98.5 97.0 93.3 94.9 100 94.2 93.3 97.7
CZP DIA DM- CLBZ
NTZ NDIA CLBZ 105 111 102 112 90.3 102 102 89.5 107 110 111 103 103 107 103 104 102 98.5 100 103 98.9 98.1 100 98.1 95.1 100 99.1 103 98.1 102 99.6 98.1 108 94.4 106 97.2
CBZ EPO- CBZ
GBP LMT LVT PGB ZNA LCA PBR 103 99.6 110 105 100 110 115 100 109
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LAB ASIA - JANUARY/FEBRUARY 2018
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