Real-Time Therapeutic Monitoring of Valproic Acid in Exhaled Breath, presented at the MSACL congress
Post-doctoral researcher Kapil Dev Singh (UKBB) presented part of his studies on therapeutic drug monitoring at the MSACL congress. They measured exhaled breath in pediatric patients treated with antiepileptic medication and compared it with the Gold Standard blood test. They identified secondary metabolites of valproic acid (VPA) and were able to predict the serum concentration of total and free VPA in real-time in a non-invasive way, using the platform SUPER SESI - Orbitrap.
Title:
Real-time therapeutic monitoring of valproic acid in exhaled breath
Authors:
Singh K (1,2), Ziesenitz V (1), Usemann J (1), Frey U (1), Van den Anker J (1), Datta AN* (1), and Sinues P* (1,2)
* shared last authors
Affiliations:
(1)University Children’s Hospital Basel, University of Basel, Basel, Switzerland
(2)Department of Biomedical Engineering, University of Basel, Basel, Switzerland
Abstract
Background:
In the field of medicine, serum concentrations of drugs with a narrow therapeutic window, used to treat seizures, are measured to assure the most efficacious and safe way of treating every individual patient. This form of personalised medicine is called therapeutic drug monitoring (TDM). We have explored the possibility to measure and monitor drugs in exhaled breath (EB) with a suitable real-time analytical method, to perform completely painless and non-invasive TDM for a future clinical application especially in pediatric patients.
Methods:
We employed SESI-HRMS to obtain highly resolved EB mass spectra. We then statistically compared these EB mass spectra between patients taking antiepileptic drugs against controls (no drugs), to find potential EB-based bio-markers for drugs. We then trained and tested various regression models to predict serum concentration of drugs using selected features from EB mass spectra. All the data analysis was performed by custom MATLAB scripts.
Results:
Our data for valproic acid (VPA), an antiepileptic agent, showed m/z at 115.1118, 132.1384, 143.1065, and 160.1331 to be significantly increased among others in patients taking VPA than controls. We hypothesize that these features correspond to proton and ammonium adduct of C7H14O, and C8H14O2, all of which were previously shown to be elevated in response to VPA. Furthermore, using EB measurements we were able to predict serum concentration of both total (RMSE ~5) and free (RMSE ~1.5) VPA in an independent group of patients (test-set). In the near future, we will perform MS/MS on selected ions to confirm their identity using exhaled breath condensate.
Conclusions:
This work is a part of an ongoing study and it is too early to come up with a definite conclusion. However, we would like to highlight the following important findings: 1) It is possible to successfully measure EB in pediatric patients treated with antiepileptic medications; 2) Several differentially abundant ions between controls and epileptic patients for various drugs were visualized (Shown for VPA here), but the identity and clinical significance of these ions is yet to be determined; 3) Serum concentration of both total and free VPA can be reasonably predicted via EB-based SESI-HRMS analysis.