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. 2025 Jan 7:15:1494646.
doi: 10.3389/fphar.2024.1494646. eCollection 2024.

LC-MS/MS assisted pharmacokinetic and tissue distribution study of ropivacaine and 3-OH-ropivacaine on rats after plane block anesthesia

Mihaela Butiulca  1   2 , Lenard Farczadi  3 , Silvia Imre  3   4 , Camil Eugen Vari  5 , Laurian Vlase  6 , Bogdan Cordos  7 , Leonard Azamfirei  1   2 , Alexandra Elena Lazar  1   2
Affiliations

LC-MS/MS assisted pharmacokinetic and tissue distribution study of ropivacaine and 3-OH-ropivacaine on rats after plane block anesthesia

Mihaela Butiulca et al. Front Pharmacol. .

Abstract

Knowledge of drug pharmacokinetics and tissue distribution is precious for ensuring patient safety and optimizing treatments. The varied use of local anesthetics, as well as the fact that anesthetics can sometimes have low therapeutic indices and numerous adverse drug reactions, makes any novel pharmacokinetics information valuable. The present manuscript describes a pharmacokinetic study of ropivacaine carried out after plane block anesthesia on an animal model, using high sensitivity, accurate, and precise LC-MS/MS bioanalysis. Both plasmatic concentrations and tissue distribution of ropivacaine and its primary active metabolite were determined. The results showed a tissue affinity of the anesthetics, a clearance of ropivacaine mainly by hepatic metabolism, and the final, mainly renal excretion of the hydroxylated metabolite. While the results cannot simply and directly be transposed to human pharmacokinetics, they offer a valuable basis for future studies and can contribute to a better understanding of the bioavailability and toxicology of the widely used modern anesthetic.

Keywords: HPLC; LC-MS/MS; pharmacokinetics; rats; ropivacaine.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Experimental protocol.
FIGURE 2
FIGURE 2
Chromatograms of ropivacaine (top) and 3-OH ropivacaine (bottom) in standard solution compared to blank samples.
FIGURE 3
FIGURE 3
Chromatograms of ropivacaine and 3-OH ropivacaine in plasma samples.
FIGURE 4
FIGURE 4
Elimination curve of ropivacaine from plasma.
FIGURE 5
FIGURE 5
Spaghetti plot of calculated tissue concentrations of ropivacaine and 3-OH-ropivacaine (concentrations are expressed in ng/g tissue, and time in hours).
FIGURE 6
FIGURE 6
Spaghetti plot of calculated tissue and plasma concentrations of ropivacaine and 3-OH-ropivacaine (concentrations are expressed in ng/g tissue, and ng/mL for plasma, and time in hours).
FIGURE 7
FIGURE 7
Maximum concentration (Cmax) of ropivacaine and 3-OH-ropivacaine in tissues and plasma (ng.mL-1).
FIGURE 8
FIGURE 8
Area under the curve to the last measurable concentration (AUClast) of ropivacaine and 3-OH-ropivacaine in tissues and plasma (ng.mL-1).
FIGURE 9
FIGURE 9
Clearance (CL) of ropivacaine and 3-OH-ropivacaine from tissues and plasma (L.h-1. kg-1).
See this image and copyright information in PMC

References

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