Comparison of Different Techniques for the Determination of Platinized Cytostatic Drugs in Urine Samples

Platinum-based cytostatic drugs are one of the most widely used cancer treatments. They are excreted via the urinary tract and can reach the environment through wastewater, posing a risk to human health due to their side effects. Four identification and quantification techniques, including liquid ch...

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Main Authors: Marina Arenas, Julia Martín, Juan Luis Santos, Irene Aparicio, Omar Fernández-Sanfrancisco, Esteban Alonso
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/27/23/8139
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author Marina Arenas
Julia Martín
Juan Luis Santos
Irene Aparicio
Omar Fernández-Sanfrancisco
Esteban Alonso
author_facet Marina Arenas
Julia Martín
Juan Luis Santos
Irene Aparicio
Omar Fernández-Sanfrancisco
Esteban Alonso
author_sort Marina Arenas
collection DOAJ
description Platinum-based cytostatic drugs are one of the most widely used cancer treatments. They are excreted via the urinary tract and can reach the environment through wastewater, posing a risk to human health due to their side effects. Four identification and quantification techniques, including liquid chromatography (LC) separation coupled to (i) a diode array ultraviolet (UV(DAD)) (ii), mass spectrometer in single ion monitoring mode (LC-MS) and (iii) multiple reaction monitoring mode (LC-MS/MS) and (iv) derivatization with diethyldithiocarbamate prior to LC-MS/MS analysis, have been optimized and compared for the multiresidue determination of main platinized cytostatic drugs (cisplatin, carboplatin, and oxaliplatin) in urine samples. Parameters that affect the efficiency of the chromatographic separation and analytical determination of different methods (column, mobile phase, wavelength, precursor ions, fragmentor, and product ions) were optimized. Analytical features, such as matrix effect, sensitivity, precision, selectivity, and linearity, were calculated. In terms of selectivity, the derivatization technique was discarded since it was only applicable to the platinated sum. A high dilution of the sample with LC-UV(DAD) was needed to reduce the matrix effect. Overall, the LC-MS/MS method presented the best analytical features (% RSD ≤ 12.8%, R<sup>2</sup> ≥ 0.991, or method-detection limits between 0.01–1 µg mL<sup>−1</sup>). The selected method was applied to the quantification of platinized cytostatic drugs in hospital urine samples from oncologic patients.
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spelling doaj.art-19c878a6f7ab4b319e3e8a7ea0e0d26b2023-11-24T11:37:16ZengMDPI AGMolecules1420-30492022-11-012723813910.3390/molecules27238139Comparison of Different Techniques for the Determination of Platinized Cytostatic Drugs in Urine SamplesMarina Arenas0Julia Martín1Juan Luis Santos2Irene Aparicio3Omar Fernández-Sanfrancisco4Esteban Alonso5Departamento de Química Analítica, Escuela Politécnica Superior, Universidad de Sevilla, C/Virgen de África 7, E-41011 Sevilla, SpainDepartamento de Química Analítica, Escuela Politécnica Superior, Universidad de Sevilla, C/Virgen de África 7, E-41011 Sevilla, SpainDepartamento de Química Analítica, Escuela Politécnica Superior, Universidad de Sevilla, C/Virgen de África 7, E-41011 Sevilla, SpainDepartamento de Química Analítica, Escuela Politécnica Superior, Universidad de Sevilla, C/Virgen de África 7, E-41011 Sevilla, SpainDepartamento de Medicina Preventiva y Salud Pública, Facultad de Farmacia, Universidad de Granada, E-18071 Granada, SpainDepartamento de Química Analítica, Escuela Politécnica Superior, Universidad de Sevilla, C/Virgen de África 7, E-41011 Sevilla, SpainPlatinum-based cytostatic drugs are one of the most widely used cancer treatments. They are excreted via the urinary tract and can reach the environment through wastewater, posing a risk to human health due to their side effects. Four identification and quantification techniques, including liquid chromatography (LC) separation coupled to (i) a diode array ultraviolet (UV(DAD)) (ii), mass spectrometer in single ion monitoring mode (LC-MS) and (iii) multiple reaction monitoring mode (LC-MS/MS) and (iv) derivatization with diethyldithiocarbamate prior to LC-MS/MS analysis, have been optimized and compared for the multiresidue determination of main platinized cytostatic drugs (cisplatin, carboplatin, and oxaliplatin) in urine samples. Parameters that affect the efficiency of the chromatographic separation and analytical determination of different methods (column, mobile phase, wavelength, precursor ions, fragmentor, and product ions) were optimized. Analytical features, such as matrix effect, sensitivity, precision, selectivity, and linearity, were calculated. In terms of selectivity, the derivatization technique was discarded since it was only applicable to the platinated sum. A high dilution of the sample with LC-UV(DAD) was needed to reduce the matrix effect. Overall, the LC-MS/MS method presented the best analytical features (% RSD ≤ 12.8%, R<sup>2</sup> ≥ 0.991, or method-detection limits between 0.01–1 µg mL<sup>−1</sup>). The selected method was applied to the quantification of platinized cytostatic drugs in hospital urine samples from oncologic patients.https://www.mdpi.com/1420-3049/27/23/8139cytostatic drugscisplatincarboplatinoxaliplatinLC-UV(DAD)LC-MS/MS
spellingShingle Marina Arenas
Julia Martín
Juan Luis Santos
Irene Aparicio
Omar Fernández-Sanfrancisco
Esteban Alonso
Comparison of Different Techniques for the Determination of Platinized Cytostatic Drugs in Urine Samples
Molecules
cytostatic drugs
cisplatin
carboplatin
oxaliplatin
LC-UV(DAD)
LC-MS/MS
title Comparison of Different Techniques for the Determination of Platinized Cytostatic Drugs in Urine Samples
title_full Comparison of Different Techniques for the Determination of Platinized Cytostatic Drugs in Urine Samples
title_fullStr Comparison of Different Techniques for the Determination of Platinized Cytostatic Drugs in Urine Samples
title_full_unstemmed Comparison of Different Techniques for the Determination of Platinized Cytostatic Drugs in Urine Samples
title_short Comparison of Different Techniques for the Determination of Platinized Cytostatic Drugs in Urine Samples
title_sort comparison of different techniques for the determination of platinized cytostatic drugs in urine samples
topic cytostatic drugs
cisplatin
carboplatin
oxaliplatin
LC-UV(DAD)
LC-MS/MS
url https://www.mdpi.com/1420-3049/27/23/8139
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AT ireneaparicio comparisonofdifferenttechniquesforthedeterminationofplatinizedcytostaticdrugsinurinesamples
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