Ultra-trace determination of oxaliplatin impurities by sweeping-MEKC-ICP-MS

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F22%3A73615369" target="_blank" >RIV/61989592:15310/22:73615369 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0026265X21010535" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0026265X21010535</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.microc.2021.106967" target="_blank" >10.1016/j.microc.2021.106967</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Ultra-trace determination of oxaliplatin impurities by sweeping-MEKC-ICP-MS

Popis výsledku v původním jazyce

Oxaliplatin represents a platinum-based cancerostatic drug that is widely used for the treatment of various types of cancer. There are two main platinum-containing impurities, impurity B and C, that can be formed as side products at very low concentrations. Their effect on biological systems can be like the oxaliplatin itself; however, this has not been fully investigated since there is a lack of methods for their determination in ultralow con-centrations. In our work, we present a method for ultra-trace determination of oxaliplatin impurities B and C, and oxaliplatin itself, using online sweeping preconcentration micellar electrokinetic chromatography coupled with inductively coupled plasma mass spectrometry (MEKC-ICP-MS). This is the first application of online pre-concentration with MEKC-ICP-MS to improve the detection limits of analytes. Under the optimal conditions, 25 mM sodium phosphate buffer at pH 2.15 with 175 mM SDS, and an injection time of 90 s at 50 mbar, baseline separation of all components within 6 min was achieved. The sweeping-MEKC-ICP-MS method was fully vali-dated in terms of linearity, limits of detection and quantification, trueness, precision, and reproducibility of migration times. Limits of detection of 2, 1, and 3 ng mL(-1) for impurity B, impurity C, and oxaliplatin, respectively, were obtained, which are 3,500-, 1,700-, and 2,100-fold lower than those for a MEKC-UV method also developed and validated as a part of this work. It also represents the detection of 98 femtograms of the impurity C (or 227 attomol of Pt) per injection. The sweeping-MEKC-ICP-MS method further benefits from a wide dynamic range up to six orders of magnitude (0.01-1,000 mu g mL(-1) for oxaliplatin) with coefficients of deter-mination greater than 0.9989. ICP-MS provides characteristic element/isotope-specific and structure-independent detection. ICP-MS helped identify the co-separated impurity B counter-ion that can be wrongly assigned as the platinum-based impurity B using standard UV detection. Finally, the validated sweeping-MEKC-ICP-MS method was applied to the analysis of oxaliplatin samples with variable impurities concentrations (0.06-1.0%). The trueness and precision ranged between 76 and 115% and 2-19%, respectively. This method allows the accurate determination of oxaliplatin impurities from 0.0003% levels; therefore, it could be used in routine pharmaceutical laboratories for quality control purposes.

Název v anglickém jazyce

Ultra-trace determination of oxaliplatin impurities by sweeping-MEKC-ICP-MS

Popis výsledku anglicky

Oxaliplatin represents a platinum-based cancerostatic drug that is widely used for the treatment of various types of cancer. There are two main platinum-containing impurities, impurity B and C, that can be formed as side products at very low concentrations. Their effect on biological systems can be like the oxaliplatin itself; however, this has not been fully investigated since there is a lack of methods for their determination in ultralow con-centrations. In our work, we present a method for ultra-trace determination of oxaliplatin impurities B and C, and oxaliplatin itself, using online sweeping preconcentration micellar electrokinetic chromatography coupled with inductively coupled plasma mass spectrometry (MEKC-ICP-MS). This is the first application of online pre-concentration with MEKC-ICP-MS to improve the detection limits of analytes. Under the optimal conditions, 25 mM sodium phosphate buffer at pH 2.15 with 175 mM SDS, and an injection time of 90 s at 50 mbar, baseline separation of all components within 6 min was achieved. The sweeping-MEKC-ICP-MS method was fully vali-dated in terms of linearity, limits of detection and quantification, trueness, precision, and reproducibility of migration times. Limits of detection of 2, 1, and 3 ng mL(-1) for impurity B, impurity C, and oxaliplatin, respectively, were obtained, which are 3,500-, 1,700-, and 2,100-fold lower than those for a MEKC-UV method also developed and validated as a part of this work. It also represents the detection of 98 femtograms of the impurity C (or 227 attomol of Pt) per injection. The sweeping-MEKC-ICP-MS method further benefits from a wide dynamic range up to six orders of magnitude (0.01-1,000 mu g mL(-1) for oxaliplatin) with coefficients of deter-mination greater than 0.9989. ICP-MS provides characteristic element/isotope-specific and structure-independent detection. ICP-MS helped identify the co-separated impurity B counter-ion that can be wrongly assigned as the platinum-based impurity B using standard UV detection. Finally, the validated sweeping-MEKC-ICP-MS method was applied to the analysis of oxaliplatin samples with variable impurities concentrations (0.06-1.0%). The trueness and precision ranged between 76 and 115% and 2-19%, respectively. This method allows the accurate determination of oxaliplatin impurities from 0.0003% levels; therefore, it could be used in routine pharmaceutical laboratories for quality control purposes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10406 - Analytical chemistry

Projekt

<a href="/cs/project/GA19-23033S" target="_blank" >GA19-23033S: Zlepšení citlivosti detekce v chirálních separacích pomocí kapilární elektroforézy ve spojení s ESI-MS nebo ICP-MS</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

MICROCHEMICAL JOURNAL

ISSN

0026-265X

e-ISSN

1095-9149

Svazek periodika

172

Číslo periodika v rámci svazku

JAN

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

6

Strana od-do

"106967-1"-"106967-6"

Kód UT WoS článku

000719818300010

EID výsledku v databázi Scopus

2-s2.0-85118726144