PMID- 38338382 OWN - NLM STAT- MEDLINE DCOM- 20240214 LR - 20240214 IS - 1420-3049 (Electronic) IS - 1420-3049 (Linking) VI - 29 IP - 3 DP - 2024 Jan 30 TI - An Automated Micro Solid-Phase Extraction (muSPE) Liquid Chromatography-Mass Spectrometry Method for Cyclophosphamide and Iphosphamide: Biological Monitoring in Antineoplastic Drug (AD) Occupational Exposure. LID - 10.3390/molecules29030638 [doi] LID - 638 AB - Despite the considerable steps taken in the last decade in the context of antineoplastic drug (AD) handling procedures, their mutagenic effect still poses a threat to healthcare personnel actively involved in compounding and administration units. Biological monitoring procedures usually require large volumes of sample and extraction solvents, or do not provide adequate sensitivity. It is here proposed a fast and automated method to evaluate the urinary levels of cyclophosphamide and iphosphamide, composed of a miniaturized solid phase extraction (microSPE) followed by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis. The extraction procedure, developed through design of experiments (DoE) on the ePrep One Workstation, required a total time of 9.5 min per sample, with recoveries of 77-79% and a solvent consumption lower than 1.5 mL per 1 mL of urine sample. Thanks to the UHPLC-MS/MS method, the limits of quantification (LOQ) obtained were lower than 10 pg/mL. The analytical procedure was successfully applied to 23 urine samples from compounding wards of four Italian hospitals, which resulted in contaminations between 27 and 182 pg/mL. FAU - Dugheri, Stefano AU - Dugheri S AUID- ORCID: 0000-0002-3078-7188 AD - Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy. FAU - Squillaci, Donato AU - Squillaci D AUID- ORCID: 0000-0001-8665-845X AD - Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy. FAU - Saccomando, Valentina AU - Saccomando V AD - Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy. FAU - Marrubini, Giorgio AU - Marrubini G AUID- ORCID: 0000-0003-1399-5783 AD - Department of Drug Sciences, University of Pavia, Via Taramelli 12, 27100 Pavia, Italy. FAU - Bucaletti, Elisabetta AU - Bucaletti E AUID- ORCID: 0000-0003-2060-5392 AD - Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy. FAU - Rapi, Ilaria AU - Rapi I AD - Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy. FAU - Fanfani, Niccolo AU - Fanfani N AD - Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy. FAU - Cappelli, Giovanni AU - Cappelli G AD - Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy. FAU - Mucci, Nicola AU - Mucci N AUID- ORCID: 0000-0003-0579-1035 AD - Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy. LA - eng PT - Journal Article DEP - 20240130 PL - Switzerland TA - Molecules JT - Molecules (Basel, Switzerland) JID - 100964009 RN - UM20QQM95Y (Ifosfamide) RN - 0 (Antineoplastic Agents) RN - 8N3DW7272P (Cyclophosphamide) RN - 0 (Solvents) SB - IM MH - Ifosfamide MH - Tandem Mass Spectrometry/methods MH - Liquid Chromatography-Mass Spectrometry MH - Biological Monitoring MH - *Antineoplastic Agents MH - Cyclophosphamide MH - Chromatography, High Pressure Liquid/methods MH - Solid Phase Extraction MH - Solvents MH - *Occupational Exposure PMC - PMC10856084 OTO - NOTNLM OT - antineoplastic drugs OT - biological monitoring OT - micro solid phase extraction OT - tandem mass spectrometry OT - ultrahigh-performance liquid chromatography OT - microSPEed COIS- The authors declare no conflicts of interest. EDAT- 2024/02/10 10:48 MHDA- 2024/02/11 16:42 PMCR- 2024/01/30 CRDT- 2024/02/10 01:08 PHST- 2023/12/28 00:00 [received] PHST- 2024/01/23 00:00 [revised] PHST- 2024/01/26 00:00 [accepted] PHST- 2024/02/11 16:42 [medline] PHST- 2024/02/10 10:48 [pubmed] PHST- 2024/02/10 01:08 [entrez] PHST- 2024/01/30 00:00 [pmc-release] AID - molecules29030638 [pii] AID - molecules-29-00638 [pii] AID - 10.3390/molecules29030638 [doi] PST - epublish SO - Molecules. 2024 Jan 30;29(3):638. doi: 10.3390/molecules29030638.