Key result
Intravenous microdialysis shows no difference in free cisplatin pharmacokinetics versus standard plasma sampling in pigs.
Why the study?
Accurate quantification of systemic free cisplatin is challenging due to its various forms in circulation, necessitating a sensitive and precise measurement method.
Mean Difference: -64.6 (95% CI -569.7–440.5)
Absolute Event Rate: 95.4% vs 160%
p-value: p=0.79
A validated LC-MS/MS method provides a reliable tool for quantifying systemic free cisplatin concentrations, demonstrating comparable pharmacokinetic parameters between standard plasma sampling and intravenous microdialysis in a porcine model.
Supports microdialysis-plasma equivalence for cisplatin PK in pigs; leaves open human translation.
Cisplatin is a potent cytotoxic agent used in the treatment of various malignancies and exerts its antitumor effect through malignant cell DNA damage and apoptosis induction. Evaluation of systemic delivery of cisplatin is important in optimization of cisplatin treatment. However, accurate quantification of systemic cisplatin is challenging due to its various forms in circulation. This study aimed to develop a sensitive (LOQ < 0.1 µg/mL) and precise Ultra Performance Liquid Chromatography (UPLC) – Tandem Mass Spectrometry (MS/MS) method for quantifying free cisplatin in microdialysates and plasma. Furthermore the aim was to compare free cisplatin concentrations measured in standard plasma samples with those obtained from intravenous microdialysis catheters in a porcine model. The method developed utilizes dichloro(ethylenediamine)platinum(II) as an internal standard that co-elutes with cisplatin, ensuring precise correction for ion suppression/enhancement effects. The method was validated, demonstrating linearity up to 100 µg/mL and good intermediate precision (CV% < 6 %) in the range of 1.0–100 µg/mL, with an LOQ of 0.03 µg/mL. The pharmacokinetic parameters (AUC0-last, Cmax, T1/2, and Tmax) showed no significant differences between the two sampling methods. This validated LC-MS/MS method provides a reliable tool for quantifying systemic free cisplatin concentrations, facilitating future systemic and local pharmacokinetic evaluations for optimization of cisplatin-based cancer treatments.
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Schmedes et al. (2024) studied Pharmacokinetic evaluation of cisplatin (n=6). Intravenous microdialysis vs. Standard plasma sampling was evaluated on AUC0-last (min•μg/mL) (Mean difference -64.6, 95% CI -569.7 to 440.5, p=0.79). Intravenous microdialysis showed no significant differences in the pharmacokinetic parameters of free cisplatin, including AUC0-last (mean difference -64.6, p=0.79), compared to standard plasma sampling in a porcine model.
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