Drug Pharmacokinetics Determined by Real‐Time Analysis of Mouse Breath

Abstract

Noninvasive, real-time pharmacokinetic (PK) monitoring of ketamine, propofol, and valproic acid, and their metabolites was achieved in mice, using secondary electrospray ionization and high-resolution mass spectrometry. The PK profile of a drug influences its efficacy and toxicity because it determines exposure time and levels. The antidepressant and anaesthetic ketamine (Ket) and four Ket metabolites were studied in detail and their PK was simultaneously determined following application of different sub-anaesthetic doses of Ket. Bioavailability after oral administration vs. intraperitoneal injection was also investigated. In contrast to conventional studies that require many animals to be sacrificed even for low-resolution PK curves, this novel approach yields real-time PK curves with a hitherto unmatched time resolution (10 s), and none of the animals has to be sacrificed. This thus represents a major step forward not only in animal welfare, but also major cost and time savings.

Numerical modeling and experimental validation of a universal secondary electrospray ionization source for mass spectrometric gas analysis in real-time

“…We have recently shown that this technique could be used to investigate the in vivo pharmacokinetics of injected drugs in mice [42]. To further illustrate the capabilities of the optimized ionizer developed here, we tested its performance towards vapors of common drugs: Melatonin, Propofol, Acetaminophen, Pentobarbital and Midazolam.…”

Gauging circadian variation in ketamine metabolism by real-time breath analysis

“…Recently, we have shown that secondary electrospray ionization (SESI) 7 coupled with high resolution mass spectrometry (HRMS) provides sufficient sensitivity and selectivity to track in vivo and in real time the metabolism of drugs in mice breath, which correlate with blood levels. 8 . The proposed method enables capturing pharmacokinetic profiles of injected drugs in real time with a time resolution of 10 s from a single mouse in a comparably stressless procedure (Fig.…”

“…The time-to-peak for this particular dose was found to be around 25-30 min, which is fully consistent with our previous results. 8 . In contrast, however, a clear difference in ketamine metabolism was observed.…”

Real-Time Quantification of Amino Acids in the Exhalome by Secondary Electrospray Ionization–Mass Spectrometry: A Proof-of-Principle Study

“…In this sense, breath analysis is gaining attention as a novel technique for clinical purposes such as diagnostics (11 ) and pharmacokinetics (12 ). Breath analysis can detect differences between individual "breathprints" which are reasonably stable over time (13 ), can be used to follow diurnal metabolic patterns (14,15 ), and is capable of quantifying hitherto unknown compounds in human breath (16,17 ).…”