Inductively Coupled Plasma Mass Spectrometry for Analysis of Metal‐Containing Pharmaceuticals

Gammelgaard, Bente; Stürup, Stefan; Møller, Charlotte

doi:10.1002/9780470921920.edm100

Cited by 4 publications

(3 citation statements)

References 103 publications

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“…To gain information on the in vivo properties of novel drugs, animal models are widely used to investigate their toxicological profile, pharmacokinetic behavior and therapeutic efficacy 11–13. Based on these data, the most promising drug candidates are then selected for further (pre)clinical development.…”

Section: Introductionmentioning

confidence: 99%

Tumor microenvironment in focus: LA-ICP-MS bioimaging of a preclinical tumor model upon treatment with platinum(iv)-based anticancer agents

et al. 2015

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The selection of drug candidates for entering clinical development relies on in vivo testing in (solid) tumor animal models. However, the heterogeneity of tumor tissue (e.g. in terms of drug uptake or tissue composition) is rarely considered when testing novel drug candidates. Therefore, we used the murine colon cancer CT-26 tumor model to study the spatially-resolved drug distribution in tumor tissue upon repetitive treatment of animals over two weeks with three investigational platinum(IV)-based anticancer agents, oxaliplatin or satraplatin. A quantitative laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) imaging method revealed a heterogeneous platinum distribution, which correlated well with the histologic features of the tumor and surrounding tissue at the microscopic level. In most of the cases, higher amounts of intratumoral platinum were found in the surrounding tissue than in the malignant parts of the sample. This indicates that determination of average platinum amounts (e.g. by microwave-assisted digestion of the sample followed by analysis with ICP-MS) might overestimate the drug uptake in tumor tissue causing misleading conclusions. In addition, we studied the platinum distribution in the kidneys of treated animals to probe if accumulation in the cortex and medulla predict potential nephrotoxicity. A 10-fold increase of platinum in the cortex of the kidney over the medulla was observed for oxaliplatin and satraplatin. Although these findings are similar to those in the platinum distribution of the nephrotoxic anticancer drug cisplatin, treatment with the compounds of our study did not show signs of nephrotoxicity in clinical use or clinical trials (oxaliplatin, satraplatin) and did not result in the alteration of renal structures. Thus, predicting the side effects based on bioimaging data by LA-ICP-MS should be considered with caution. To the best of our knowledge, this is the first LA-ICP-MS study on spatially-resolved platinum accumulation in tissues after repetitive platinum-based anticancer drug treatment of mice bearing a preclinical tumor model.

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Section: Introductionmentioning

confidence: 99%

Tumor microenvironment in focus: LA-ICP-MS bioimaging of a preclinical tumor model upon treatment with platinum(iv)-based anticancer agents

et al. 2015

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“…the interaction of metallodrugs with serum proteins, 18–21 protein binding kinetics, the reversibility of protein binding and the investigation of hydrolysis products and metabolites of metallodrugs 22 on a qualitative and/or quantitative basis. 23–25…”

Section: Introductionmentioning

confidence: 99%

The impact of whole human blood on the kinetic inertness of platinum(iv) prodrugs – an HPLC-ICP-MS study

et al. 2018

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“…These non-selective techniques include phosphorescence [18], X-ray fluorescence [19], atomic absorption spectroscopy (AAS) [20][21][22] and inductively coupled plasma-mass spectrometry (ICP-MS) [23][24][25]. ICP-MS is the most frequently used tool for the measurement of total platinum for the drug cisplatin [14,26]. However, circulating total platinum represents a mixture of platinum species, with differing biological activity and toxicity profiles.…”

Section: Introductionmentioning

confidence: 99%

Zwitterionic hydrophilic interaction liquid chromatography-tandem mass spectrometry with HybridSPE-precipitation for the determination of intact cisplatin in human plasma

Xie

Colin

Bocxlaer

2017

Talanta

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Cisplatin is a first-line chemotherapeutic for the treatment of a wide variety of cancers since its discovery in the 1960s. Although various techniques have been reported for the measurement of total platinum in biological matrices, such as inductively coupled plasma-mass spectrometry and derivatization procedures, a specific, sensitive and robust assay for the quantification of intact cisplatin is still lacking. Therefore, we present a rapid, selective, sensitive, and reliable UHPLC-MS/MS based method for the determination of intact cisplatin in human plasma in support of a Phase II clinical trial. The optimal chromatographic behavior of cisplatin was achieved on a Syncronis HILIC column (50 × 2.1mm, 1.7µm, zwitterionic stationary phase). The retention behavior of cisplatin on this zwitterion-based stationary phase was well described by an adsorptive interaction model. A simple sample preparation based on protein precipitation combined with the removal of phospholipids by HybridSPE-precipitation was developed. The method was proven to be free of a relative matrix effect. The assay was validated within a range of 20 - 10,000ng/mL using 100μL of plasma sample. The intra and inter-day precisions were all less than 7.6%, and none of the bias was greater than 13.1%, thus corroborating that the developed method is precise and accurate. As a proof of concept, the assay has been successfully applied to plasma samples obtained from different patients who were enrolled in the Phase II trial and were treated with cisplatin.

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Inductively Coupled Plasma Mass Spectrometry for Analysis of Metal‐Containing Pharmaceuticals

Cited by 4 publications

References 103 publications

Tumor microenvironment in focus: LA-ICP-MS bioimaging of a preclinical tumor model upon treatment with platinum(iv)-based anticancer agents

Tumor microenvironment in focus: LA-ICP-MS bioimaging of a preclinical tumor model upon treatment with platinum(iv)-based anticancer agents

The impact of whole human blood on the kinetic inertness of platinum(iv) prodrugs – an HPLC-ICP-MS study

Zwitterionic hydrophilic interaction liquid chromatography-tandem mass spectrometry with HybridSPE-precipitation for the determination of intact cisplatin in human plasma

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