MSACL 2024 Abstract

Development and Validation of a Novel LC/MS-MS Method for the Simultaneous Quantification of 16 Drugs for Therapeutic Drug Monitoring

Jessica J. Miller (1,2), Eric Pham (2), Kerene Brown (2), Edmon Ang (2), Edward Dunn (2)
(1) University Health Network, Toronto, ON, Canada (2) Dynacare, Brampton, ON, Canada

Jessica Miller, PhD Chemistry, CACB fellow (Presenter) University Health Network

Relevant Financial Disclosures (within past 24 months, reported on Jan 16, 2024) No relevant financial relationship(s) to disclose. Conflict mitigation NOT REQUIRED.

Objectives: Therapeutic drug monitoring (TDM) involves the measurement of a drug in a patient’s blood in order to tailor dosages and maintain therapeutic efficacy. Drugs that benefit from TDM have narrow therapeutic ranges, exhibit pharmacokinetic variability, and/or are used for an extended period of time. Anti-epileptic and anti-psychotic drugs are both examples wherein the drug classes are broad and often prescribed in combination, and may require lifelong treatment for symptom management. Adverse effects of anti-epileptic and anti-psychotic drugs are well known, therefore TDM is important for patient safety. However, due to the large size of these drug classes, polypharmaceutical nature of treatment, and disparate concentrations of the drugs in serum, monitoring of anti-epileptic and anti-psychotic drugs is challenging. This study developed and validated a method for the simultaneous quantification of 16 anti-epileptic and anti-psychotic drugs in human serum using liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Methods: We developed and validated a rapid LC-MS/MS method for the simultaneous quantification of anti-epileptic and anti-psychotic drugs including 9-OH-risperidone/Risperidone, Clobazam/Norclobazam, Clozapine/Norclozapine, Ethosuximide, Gabapentin, Lamotragine, Levetiracetam, MHC, Phenobarbital, Pregabalin, Primidone, Quietiapine, and Topiramate in serum on the SCIEX Triple Quad 4500. Sample preparation includes a protein precipitation protocol. The calibration and quality control ranges were chosen to cover the entire therapeutic range for the respective drugs. The analytical evaluation included linearity, imprecision, accuracy, method comparison, limit of quantitation (LoQ), ion suppression, and matrix effects.

Results: The total run time was ≤ 5 minutes. Intra- and inter-day imprecision ranged from 2.7%-8.0% and 3.3%-13.3% respectively. All of the criteria set according to relevant guidelines for lab developed tests passed for linearity, accuracy, and method comparison. LoQ ranged from 4.48 µmol/L (Phenobarbital) to 3.10 nmol/L (9-OH-risperidone). No significant ion suppression or matrix effects were observed.

Conclusion: This method is suitable for therapeutic drug monitoring of indicated anti-epileptic and anti-psychotic drugs in patients undergoing mono- or polytherapy.