Key result
IV cisplatin accumulates more in rat kidneys than liver, indicating primary renal excretion.
Why the study?
A validated method for quantitative determination and distribution of cisplatin in rat kidney and liver tissues was needed to provide essential pharmacological and clinical information.
A newly validated LC/ESI-MS/MS method demonstrated that intravenously administered cisplatin primarily accumulates in the kidney compared to the liver in a rat model.
Validated LC-MS/MS method enables cisplatin tissue quantification in rats; leaves open human pharmacokinetic translation.
A sensitive and rapid liquid chromatography positive ion electrospray ionization tandem mass spectrometric (LC/ESI-MS/MS) method has been developed and validated for the quantitative determination and distribution of cisplatin (CP) in kidney and liver tissues after intravenous administration of drug to adult male Sprague Dawley rats. Oxaliplatin (OXP) was used as an internal standard. The tissue samples were homogenized and extracted using conventional liquid-liquid extraction method with phosphate buffer containing ethyl acetate and then subjected to LC-MS analysis. The chromatographic separation was achieved on an Agilent ZORBAX SB C-18 column (50 × 2.1 mm, 1.8 µm) using the mobile phase consisting of 0.1% formic acid in water (Solvent A) : methanol (Solvent B) (40 : 60; v/v) in an isocratic elution followed by detection with positive ion electrospray ionization tandem mass spectrometry using the transitions of m/z 301 > 265 for CP and m/z 398 > 310 for OXP in multiple reaction monitoring mode. The calibration curve was linear in the range of 5.0-7000 and 10.0-6000 ng/ml for kidney and liver tissue homogenates, respectively. The method revealed good performances in terms of within-batch, between-batch precision (1.31-5.70%) and accuracy (97.0-102.24%) for CP in both kidney and liver tissue homogenates including lower and upper limits of quantification. The recoveries from spiked control samples were >81.0% and >87.0 % for CP and OXP, respectively. Matrix effect was found to be negligible, and the stability data were within the acceptable limits. Further, the validated LC/ES-MS/MS method was successfully applied to investigate the distribution of CP in kidney and liver tissues after intravenous administration of CP to male Sprague Dawley rats. The results showed that the higher amount of CP was distributed in kidney followed by liver, which indicated that CP mainly accumulated in kidney tissues and renal excretion might be a primary and main elimination route. This is the first research approach focused on the quantitative determination and distribution of CP in rat kidney and liver tissue homogenates by using LC/ESI-MS/MS, which could provide essential information for further pharmacological and clinical studies of CP.
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Bandu et al. (2015) studied this question. Cisplatin was evaluated on Distribution of cisplatin in kidney and liver tissues. Following intravenous administration in male Sprague Dawley rats, cisplatin accumulated in higher amounts in kidney tissues compared to liver, indicating renal excretion as a primary elimination route.
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