title: Nanoparticle-assisted MALDI-TOF MS combined with seed-layer surface preparation for quantification of small molecules.
abstract: Despite the advantages of simplicity and high-throughput detection that matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has over other methods, quantitative analysis of low-molecular-weight analyte is hampered by interference from matrix-derived background noise and signal fluctuation due to the inhomogeneous MALDI sample surface. Taking advantage of improved sample homogeneity through matrix-conjugated magnetic nanoparticles (matrix@MNP) and the seed-layer method, we report a new strategy for the rapid identification and quantification of drugs in urine samples, using morphine and 7-aminoflunitrazepam (7-aminoFM2) as model compounds. To our knowledge, this is the first attempt using the seed-layer method for small molecule analysis. By applying the proposed seed-layer method, which was specifically optimized for the 2,5-dihydroxybenzoic acid@MNP (DHB@MNP) matrix, homogeneous sample crystallization examined by microscopy analysis was obtained that generated reproducible MALDI signals (RSD<10.0%). For urine sample analysis, simple liquid-liquid extraction as a sample pretreatment step effectively reduced the ion suppression effect caused by the endogenous components in urine; good recoveries (82-90%) were obtained with a small ion suppression effect (<14% of signal decrease). This newly developed method demonstrated good quantitation linearity over a range of 50-2000 ng mL(-1) (R(2)>0.996) with reduced signal variation (RSD<10.0%). The detection limit is 30 ng mL(-1) with good precision (intra-day, 2.0-9.3%; inter-day, 5.0-10.0%) and accuracy (intra-day, 95.0-106.0%; inter-day, 103.0-115.5%). The nanoparticle-assisted MALDI-TOF MS combined with seed-layer surface preparation provides a rapid, efficient and accurate platform for the quantification of small molecules in urine samples.
authors.affiliation: Department of Chemistry, Soochow University, Taipei, Taiwan.
authors.forename: Yi-Chi
authors.initials: YC
authors.lastname: Ho
authors.forename: Mei-Chun
authors.initials: MC
authors.lastname: Tseng
authors.forename: Ying-Wei
authors.initials: YW
authors.lastname: Lu
authors.forename: Chun-Cheng
authors.initials: CC
authors.lastname: Lin
authors.forename: Yu-Ju
authors.initials: YJ
authors.lastname: Chen
authors.forename: Ming-Ren
authors.initials: MR
authors.lastname: Fuh
mesh_terms: D053000:Analytic Sample Preparation Methods; D005591:Chemical Fractionation; D005240:Feasibility Studies; D005445:Flunitrazepam / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000652:urine; D005841:Gentisates / Q000737:chemistry / Q000302:isolation & purification; D057230:Limit of Detection; D016014:Linear Models; D008280:Magnetics; D008970:Molecular Weight; D009020:Morphine / Q000302:isolation & purification / Q000652:urine; D053758:Nanoparticles / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000302:isolation & purification / Q000652:urine*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D013499:Surface Properties; D053719:Tandem Mass Spectrometry; D016482:Urinalysis / Q000379:methods*
chemical_list: D005841:Gentisates; D004364:Pharmaceutical Preparations; D005445:Flunitrazepam; D009020:Morphine; C036343:7-aminoflunitrazepam; C010925:2,5-dihydroxybenzoic acid