Investigation of endogenous blood plasma phospholipids, cholesterol and glycerides that contribute to matrix effects in bioanalysis by liquid chromatography/mass spectrometry

Ismaiel, Omnia A.; Zhang, Tianyi; Jenkins, Rand; Karnes, H. Thomas

doi:10.1016/j.jchromb.2010.10.012

Cited by 132 publications

(83 citation statements)

References 30 publications

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“…Samples with elevated concentrations of phospholipids, such as glycerophosphocholines and lysophosphatidylcholines, exhibit increase in ionization suppression when compared to normal plasma [55]. Lipid-related interference is generally not an issue with immunocapture-based methods, but it can be source of concern with methods that use nonselective isolations such as partial protein precipitation.…”

Section: Mass Spectrometric Detectionmentioning

confidence: 99%

Internal Standards for Absolute Quantification of Large Molecules (Proteins) from Biological Matrices by LC-MS/MS

Faria¹,

Halquist²

2018

Calibration and Validation of Analytical Methods - A Sampling of Current Approaches

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Internal standardization plays a critical role in the performance of a bioanalytical method. There has been a tremendous increase in the popularity of using liquid chromatography tandem mass spectrometry (LC-MS/MS) methods for quantitative bioanalysis of protein molecules. Protein, being too large to be directly analyzed by LC-MS/MS, is proteolyzed and a characteristic peptide is used as a surrogate analyte for quantification. Internal standardization in small molecules' analysis is straightforward, i.e., either a stable labeled isotope (SIL) form of the analyte or a structural analogue is used. As protein quantification involves protein digestion to yield peptides, there are more options for internal standardization. Currently, internal standard selection is based on the availability of the internal standards and the sample preparation workflow. A SIL-form of the analyte protein is the ideal internal standard. However, its use is limited due to cost and commercial availability. Alternatively, a SIL form the surrogate peptide analyte or a cleavable SIL-peptide can be used as an IS. For preclinical bioanalysis of humanized IgG antibody-based drugs, a universal SIL analogue protein has been effectively used as an internal standard. This chapter focuses on internal standardization for the quantitative analysis of proteins, such as biotherapeutics and biomarkers, using LC-MS/MS.

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Section: Mass Spectrometric Detectionmentioning

confidence: 99%

Internal Standards for Absolute Quantification of Large Molecules (Proteins) from Biological Matrices by LC-MS/MS

Faria¹,

Halquist²

2018

Calibration and Validation of Analytical Methods - A Sampling of Current Approaches

View full text Add to dashboard Cite

show abstract

“…Some exogenous and endogenous matrix effects are well known and have been described in literature, but many remain undetermined and are rarely explored in detail. A limited number of extensive and systematic studies have been performed to assess the broad nature of matrix effects providing much needed information regarding mechanisms of matrix effects in general and methods for their elimination (Chambers et al, 2007;Ismaiel et al, 2010;Little et al, 2006;Mallet et al, 2004;Marchi et al, 2010;Muller et al, 2002;Tong et al, 2002;Xu et al, 2005). In contrast, most of the current knowledge is based on studies focused on specific matrix effects.…”

Section: Sources Of Matrix Effectsmentioning

confidence: 99%

“…In addition, phospholipids contain one or two fatty acid esters that are responsible for the hydrophobicity of phospholipids. In general, ACN extracts contain significantly lower amounts of residual lipids than methanol or acetone extracts (Chambers et al, 2007;Ismaiel et al, 2010). LLE can provide cleaner samples, but lipid separation depends heavily on pH and organic solvents used for the extraction (Chambers et al, 2007;Ismaiel et al, 2010;Muller et al, 2002).…”

Section: Plasmamentioning

confidence: 99%

“…In general, ACN extracts contain significantly lower amounts of residual lipids than methanol or acetone extracts (Chambers et al, 2007;Ismaiel et al, 2010). LLE can provide cleaner samples, but lipid separation depends heavily on pH and organic solvents used for the extraction (Chambers et al, 2007;Ismaiel et al, 2010;Muller et al, 2002). Non-polar lipids such as triacylglycerols, cholesterol, and cholesterol esters have good solubility in hexane, chloroform, and ethers and will be extracted with these solvents from plasma.…”

Section: Plasmamentioning

confidence: 99%

“…Therefore, it is important to determine which lipids lead to matrix effects and select solvents for LLE or SPE that will not extract these lipids. Since phospholipids are more likely to lead to pronounced matrix effects, the use of less polar solvents, such as methyl tert-butyl ether (MTBE) and MTBE-hexane mixtures for LLE can help to minimize matrix effects caused by phospholipids (Bennett and Liang, 2004;Ismaiel et al, 2010). Similar considerations apply to SPE sample clean-up, but derivatized solid-phase columns can provide efficient phospholipid removal (Aurand and Trinh, 2009;Chambers et al, 2007).…”

Section: Plasmamentioning

confidence: 99%

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