7


Tables Table 1: Targeted drugs in TDM


Class Antibiotics Drugs


Amikacin, Amoxicillin, Azithromycin, Cefixime, Cefoperazone, Cefuroxime, Cephalexin, Clarithromycin, Clavulanic acid, Clindamycin, Colistin A and B, Daptomycin, Erythromycin, Ethambutol, Gentamicin, Isoniazid, Levofloxacin, Neomycin, Pyrazinamide, Rifampicin, Sublactam, Sulfamethoxazole, Tobramycin, Trimethoprim, Vancomycin.


Anticonvulsants


Carbamazepine, Clobazam, Clonazepam, Clorazepate, Diazepam, Eslicarbazepine acetate, Ethosuximide, Ezogabine (Retigabine), Felbamate, Gabapentin, Lacosamide, Lamotrigine, Levetiracetam, Lorazepam, Midazolam, Nitrazepam, Nordiazepam, Oxcarbazepine, Perampanel, Phenobarbital, Phenytoin, Pregabalin, Primidone, Progabide, Rufinamide, Stiripentol, Tiagabine, Topiramate, Trimethadione, Valproic acid, Vigabatrin, Zonisamide.


Antidepressants


Amisulrpide, Aripiprazole, Citalopram, Clozapine, Doxepin, Duloxetine, Escitalopram, Fluoxetine, Flupentixol, Fluvoxamine, Haloperidol, Mianserin, Mirtazapine, Moclobemide, Nordoxepin, Norfluoxetine, Nortriptyline, Olanzapine, Paroxetine, Pimozide, Prochlorperazine, Quetiapine, Risperidone, Sertraline, Trazodone, Tryptophan, Venlafaxine, Zuclopenthixol.


Antifungals Anticancer drugs


Amphotericin B, Anidulafungin, Caspofungin, Fluconazole, Iodiconazole, Isavuconazole, Itraconazole, Micafungin, Posaconazole, Voriconazole.


Busulfan, Carboplatin, Docetaxel, Erlotinib, Gefitinib, Ifosfamide, Imatinib, Irinotecan, Lapatinib, Lenalomide, Melphalan, Methotrexate, Nilotinib, Paclitaxel, Pemetrexed, Procarbazine, Raltitrexed, Sorafenib, Sunitinib, Tamoxifen, Tegafur, Thalidomide, Vinblastine, Vincristine.


Anti-viral drugs


Abacavir, Amprenavir, Atazanavir, Darunavir, Delavirdine, Didadosine, Efavirenz, Emtricitabine, Etravirine, Fosamprenavir, Ganciclovir, Indinavir, Lamivudine, Lopinavir, Maraviroc, Nelfinavir, Nevirapine, Raltegravir, Ribavirin, Ritonavir, Saquinavir, Stavudine, Tenofovir, Tipranavir, Valganciclovir, Viramidine, Zalcitabine, Zidovudine.


Cardioactive drugs Immunosuppressants


Acetyldigitoxin, Amiodarone, Deslanoside, Digitoxin, Digoxin, Methyldigoxin, Lanatoside, Rivaroxaban


Cyclosporine, Everolimus, Mycophenolate glucuronide, Mycophenolic acid, Sirolimus, Tacrolimus.


Table 2: MS/MS parameters for immunosuppressants Parameter


Value System Ionisation


Acquisition Mode Transitions


: LCMS-8050 : Heated ESI : MRM


: Compound 13C2 D4 13CD3 13CD4


Everolimus -Everolimus Sirolimus -Sirolimus Tacrolimus -Tacrolimus


D12


Ion Source Temperature


Ion Source Gas Flow CID Gas Pressure


Cyclosporin A -Cyclosporin A


: Interface 200°C


: Heating gas 10 L/min : 270 kPa


MRM


975.6 > 908.5 981.5 > 914.5 931.6 > 864.5 935.4 > 864.5 821.5 > 768.6 826.4 > 773.6


1219.9 > 1202.8 1231.8 > 1214.9


Heating block 200°C


Drying gas 10 L/min


CE (V) Dwell time (ms)


20 20 18 18 22 22 21 21


59 59 59 59 59 59 59 59


Desolvation line 250°C


Nebulising gas 3 L/min


CID Gas Pressure Pause Time


Polarity Switching


Table 3: Immunosuppressant QC Results Level (ng/mL)


Cyclosporin A Low (30.5) Everolimus


Mid-low (260.1) Mid-High (1172.8) High (1432.8) Low (2.8)


Sirolimus


Mid-low (7.2) Mid-High (30.5) High (38.1) Low (3)


Tacrolimus


Mid-low (7.5) Mid-High (29.5) High (36.6) Low (2.7)


Mid-low (6.9) Mid-High (28.9) High (36.2)


%RSD 2.4% 7.2% 3.5% 9.9% 7.9% 7.0% 4.2% 8.9% 15% 8.0% 5.4% 11% 9.1% 5.4% 3.2% 3.9%


Accuracy 80.0% 86.0% 93.6% 93.2% 88.2% 97.4% 94.2% 93.4% 87.0% 93.6% 96.0% 96.5% 99.5% 97.0% 99.0% 98.0%


Table 4: Targeted anticonvulsant drugs Compound Name


Acronym


Class


Calibration Range


Carbamazepine


Carbamazepine-10,11-epoxide Gabapentin Lacosamide Lamotrigine Levetiracetam Phenobarbital Phenytoin Pregabalin Topiramate Valproic acid Zonisamide Clobazam


Clonazepam Diazepam


N-Desmethylclobazam Nitrazepam Nordiazepam


CBZ


EPO-CBZ GBP LCA LMT LVT PBR PNT PGB TPA VPA ZNA


CLBZ CZP DIA


DM-CLBZ NTZ


NDIA


Carboxamide Carboxamide


GABA analogue


Modified amino acid Triazine


Pyrrolidine Barbiturate Hydantoin


GABA analogue Fructose derivative Fatty acid


Sulphonamide Benzodiazepine Benzodiazepine Benzodiazepine Benzodiazepine Benzodiazepine Benzodiazepine


(mg/L) LLOQ 1


2 1


0.8 1 4 3 1


0.5 1 8 3


0.05


0.005 0.1


0.06 0.02 0.08


ULOQ 20 45 30 15 25 70 50 30 10 20


120 45


0.7


0.07 2.5 4.5 0.3 1.2


Table 5: MS common parameters for anticonvulsants Parameter


Value System Ionisation Acquisition Mode


Ion Source Temperature


Ion Source Gas Flow


: LCMS-8050 : Heated ESI : MRM


: Interface 300°C : Heating gas 10 L/min


: 270 kPa : 1 ms : 5ms


Heating block 400°C Drying gas 10 L/min Desolvation line 150°C Nebulising gas 3 L/min


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