Abstract

Platinum-based antineoplastic drugs (PtADs) are among the most important and used families of chemotherapy drugs, which, even showing severe side effects and being hindered by drug resistance, are not likely to be replaced clinically any time soon. The growing interest in the occupational health community in antineoplastic drug (AD) surface contamination requires the development of increasingly fast and easy high-throughput monitoring methods, even considering the lack of harmonized legally binding regulation criteria. Thus, a wipe sampling method together with zwitterionic hydrophilic interaction liquid chromatography (HILIC-Z)–tandem mass spectrometry (MS/MS) analysis was developed for the simultaneous evaluation of oxaliplatin, cisplatin, and carboplatin surface contaminations. A design of experiments approach was used to optimize the chromatographic conditions. Limits of quantification ranging from 2 to 5 ng/mL were obtained from interday and intraday repetitions for oxaliplatin and carboplatin, and between 170 and 240 ng/mL for cisplatin. The wipe desorption procedure is equivalent to other AD sampling methods, enabling a fast sample preparation, with an LC-MS/MS analysis time of less than 7 min.

Highlights

  • During the last 50 years, oncology has gone through remarkable changes, resulting in transforming malignant germ-cell testicular tumors from highly fatal to nearly uniformly cured neoplasms [1,2]

  • We report on a shell particle–zwitterionic–hydrophilic interaction chromatography (HILIC) LC-MS/MS method developed and validated to determine oxaliplatin, cisplatin, and carboplatin

  • The factors selected were the content of organic in the mobile phase (ACN from 85 to 90%), the amount of ammonium formate (FA, from 5 to 20 mM), the pH of the aqueous mobile phase (3.0 to 7.0), and the column compartment temperature

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Summary

Introduction

During the last 50 years, oncology has gone through remarkable changes, resulting in transforming malignant germ-cell testicular tumors from highly fatal to nearly uniformly cured neoplasms [1,2]. Cisplatin was accepted for pharmacological use in 1978, and since 25 platin drugs have entered clinical trials. Both the “second generation” and “third generation” of platinum-based antineoplastic drugs (PtADs), respectively, carboplatin, approved by the United States (US) Food and Drug Administration (FDA) as Paraplatin in 1989 [9], and oxaliplatin, authorized for clinical use in the European Union in 1999 and the US in 2002 [10], gained broadly worldwide compliance. The development of Pt-based drugs aimed to reduce toxicity, increase compound stability, and extend the application to different kinds of cancer. Among all the molecules synthesized and evaluated, carboplatin, thanks to its broader therapeutic index and reduced toxicity, was interesting. The greater stability of carboplatin is given by the chelating (cyclobutanedicarboxylate) ligand

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