2014
DOI: 10.1039/c4an00094c
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Recent advances in sample preparation techniques to overcome difficulties encountered during quantitative analysis of small molecules from biofluids using LC-MS/MS

Abstract: Liquid chromatography-mass spectrometry analysis of small molecules from biofluids requires sensitive and robust assays. Because of the very complex nature of many biological samples, efficient sample preparation protocols to remove unwanted components and to selectively extract the compounds of interest are an essential part of almost every bioanalytical workflow. This review describes the most common problems encountered during sample preparation, ways to optimize established sample preparation techniques an… Show more

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Cited by 225 publications
(111 citation statements)
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References 164 publications
(178 reference statements)
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“…The most common solvents used in LLE are mixtures of chloroform, methanol and water (in differing ratios), but chloroform is often replaced with dichloromethane now owing to its lesser toxicity, with similar results (Reis et al, 2013). Modifications of LLE solvent include using additives such as acetic acid, hydrochloric acid, formic acid, citric acid, ethyl acetate and n-butyl chloride, as well as replacing chloroform with MTBE or butanol (Bylda et al, 2014;Jemal et al, 2010;Teo et al, 2015). Most of these modifications are specific to the analyte in question or are for the purpose of combatting matrix effects from a particular species of PL, further supporting the need to individualize the solvent and system used (Michopoulos et al, 2011).…”
Section: Methods Of Pl Removal Prior To Analysismentioning
confidence: 98%
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“…The most common solvents used in LLE are mixtures of chloroform, methanol and water (in differing ratios), but chloroform is often replaced with dichloromethane now owing to its lesser toxicity, with similar results (Reis et al, 2013). Modifications of LLE solvent include using additives such as acetic acid, hydrochloric acid, formic acid, citric acid, ethyl acetate and n-butyl chloride, as well as replacing chloroform with MTBE or butanol (Bylda et al, 2014;Jemal et al, 2010;Teo et al, 2015). Most of these modifications are specific to the analyte in question or are for the purpose of combatting matrix effects from a particular species of PL, further supporting the need to individualize the solvent and system used (Michopoulos et al, 2011).…”
Section: Methods Of Pl Removal Prior To Analysismentioning
confidence: 98%
“…Most of these modifications are specific to the analyte in question or are for the purpose of combatting matrix effects from a particular species of PL, further supporting the need to individualize the solvent and system used (Michopoulos et al, 2011). For example, with highly hydrophilic compounds that are not easily recovered through LLE, adding high concentrations of salt to increase the polarity of the aqueous phase while using a water-miscible solvent can lead to superior phase separation, aiding in quantification of analytes from biological samples in a process referred to as salt-assisted LLE or SALLE (Bylda et al, 2014). In a 2008 review, Srinivas cautioned against discarding a possible LLE solvent based on its reputation for enhancing matrix effects (Srinivas, 2009).…”
Section: Methods Of Pl Removal Prior To Analysismentioning
confidence: 99%
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“…[7] We applied different protein precipitation/extraction methods using methanol, acetonitrile, and methyl tert-butyl ether (MTBE) as a precipitation/extraction solvent. Methanol and acetonitrile had effectively removed most of plasma proteins.…”
Section: Sample Preparationmentioning
confidence: 99%