Monolithic packed 96‐tips set for high‐throughput sample preparation: determination of cyclophosphamide and busulfan in whole blood samples by monolithic packed 96‐tips and LC‐MS

Abstract

A monolithic methacrylate packed 96-tips device was used for the extraction of the busulfan and cyclophosphamide in whole blood samples. Using a packed 96-tips set, a 96-well plate could be handled in about 2 min. The key aspect of the monolithic phase is that monolithic material can offer both good extraction capacity and low-back-pressure properties. The validation of the methodology showed that the accuracy values of quality-control samples were between 99 and 113% for busulfan, and between 103 and 110% for cyclophosphamide. The inter-day precision ranged from 7.0 to 12% for busulfan and from 13 to 16% for cyclophosphamide. The standard calibration curves were obtained within the concentration range 5-2000 nm for busulfan and from 10 to 5000 nm for cyclophosphamide in blood samples. The coefficients of determination were ≥0.99.

Fabrication of a GMA-co-EDMA Monolith in a 2.0 mm i.d. Polypropylene Housing

“…When a plastic housing, such as polypropylene (PP) or cyclic olefin copolymer (COC), is used then the surface attachment to the housing is somewhat more challenging due to the hydrophobicity and low reactivity of polyolefines. PP is particularly popular as a housing for polymer monoliths in SPE applications and formats have included pipette-tips [2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20] and syringe filters [21]. These monoliths have been used for the pre-concentration of peptides [2,8,10,11,15,16,18], proteins [5,20], fungicides [12], pesticides [3,4], plant flavones [7], pharmaceuticals [6,9,13,14,17] alkaloids [19], and metals [21] and fabrication protocols using pipette-tips have been reviewed by Blomberg [21] and Altun [22].…”

Butyl Methacrylate-Co-Ethylene Glycol Dimethacrylate Monolith for Online in-Tube SPME-UHPLC-MS/MS to Determine Chlopromazine, Clozapine, Quetiapine, Olanzapine, and Their Metabolites in Plasma Samples

“…Although the proposed monolith synthesis was based on classical radicalar procedures [19,20], the innovation of this work is related to direct coupling of the poly (butyl methacrylate-co-ethylene glycol dimethacrylate monolith capillary (in-tube SPME) to the LC-MS/MS system.…”

“…As reported in the literature, the poly(butyl methacrylate-co-ethylene glycol dimethacrylate) monolith is selective for hydrophobic analytes, such as polycyclic aromatic hydrocarbons in smoked meat products [19] and cyclophosphamide and busulfan in whole blood samples [20].…”

Modern Approaches to Preparation of Body Fluids for Determination of Bioactive Compounds

“…In both cases, sample preparation was performed in only about 2 min for 96 samples. However, in the case of whole-blood analysis, the monolithic packed 96 tips can be re-used up to only five times, inferior to the 100 times achieved with MEPS methodology [45]. Comparing the determination of the beta-blockers in plasma, using monolithic packed 96 tips, with the protein precipitation method (using 0.1% formic acid in acetonitrile), the tips method resulted in a higher (2-3 times) S/N ratio.…”

“…Two automated clean-up methodologies, based on monolithic packed 96-tip sets and combined with LC-MS/MS, were employed for determination of the beta-blockers (pindolol and metoprolol) in plasma [44] and anti-cancer drugs (cyclophosphamide and busulfan) in whole-blood samples [45]. In the case of the beta-blocker analysis, a 100-µL sample volume was handled, and, for the determination of the anti-cancer drugs, 1 mL of a sample was needed.…”