A Direct Injection LC/ESI-MS/MS Analysis of Urinary Cyclophosphamide as an Anticancer Drug for Monitoring Occupational Exposure

Abstract

A highly sensitive and reliable analytical method that uses liquid chromatography/electrospray ionization tandem mass spectrometry coupled with a simple on-line solid-phase extraction was developed to monitor occupational exposure by measuring cyclophosphamide in the urine of medical staffs who handle this anticancer drug. The quantitation limit is 3 pg/mL with a signal-to-noise ratio of more than 10, and the measurement range is 3 pg/mL to 3 ng/mL. Using this method, trace levels of cyclophosphamide have been detected in the urine of two pharmacists after handling this anticancer drug during more than 4 years exposure survey. This finding strongly suggests that it is very important to monitor the occupational exposure of medical staffs who handle anticancer drugs in order to assess the health hazard and control the use of these chemotherapies. These data also show that this analytical method can be successfully used to monitor occupational exposure by measuring the levels of residual cyclophosphamide in human urine.

Protonated and Sodiated Cyclophosphamide Fragmentation Pathways Evaluation by Infrared Multiple Photon Dissociation Spectroscopy

“…Korany and co-workers, in 2022, investigated the protonated CP fragmentation by ESI–MS and quantum mechanics . In this work, they reported fragments observed earlier in the literature and presented theoretical calculations to reason the structures proposed, confirming previous propositions. − , …”

“…As reported by Maekawa et al and Bai et al, the chlorine isotopic distribution allows the structural elucidation of these species. It was observed by mass selecting specific isotope distributions that the [CP + H] + species with two 35 Cl ( m / z 261) alone was the origin of both fragments.…”

“…In the specific case of CP, Maekawa and co-workers presented some putative structures for the species formed under collision-induced dissociation (CID) from protonated CP based on the isotopic patterns of the chloride atoms and isotopically marked CP. High-resolution MS (HRMS) results from Verscheure and co-workers that also evaluated cyclophosphamide-d4 have confirmed these results …”

“…26 In this work, they reported fragments observed earlier in the literature and presented theoretical calculations to reason the structures proposed, confirming previous propositions. [23][24][25]27 To the best of the authors' knowledge, there have been no comprehensive experimental investigations conducted to verify the nature of the fragments' structures, notwithstanding these prior studies on the protonated and sodiated CP fragmentation pattern.…”

Development of a Highly Sensitive and Rapid Liquid Chromatography–Tandem Mass Spectrometric Method Using a Basic Mobile Phase Additive to Determine the Characteristics of the Urinary Metabolites for Niemann–Pick Disease Type C

“…Column switching was used as the LC system in this study. 26,27,29,54) After injection of the diluted sample, a 20 mmol/L ammonium acetate solution/ methanol (9 : 1, v/v) mixture was loaded onto an OASIS HLB column for pretreatment (2.1 mm i.d. × 20 mm, 5 µm, Waters, Milford, MA, U.S.A.).…”