Ion-suppression effects in liquid chromatography–tandem mass spectrometry due to a formulation agent, a case study in drug discovery bioanalysis

Larger, Patrice; Breda, Massimo; Fraier, Daniela; Hughes, Heather; James, Christopher

doi:10.1016/j.jpba.2005.03.009

Cited by 80 publications

(41 citation statements)

References 19 publications

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“…Conversely, when 0.1% Tween 80 was used as a vehicle, 50-80% ion suppression was observed for both iv and po administration routes (Xu et al, 2005). These results are supported by several other researchers (Larger et al, 2005;Shou and Naidong, 2003;Tong et al, 2002). Moreover, polysorbates including Tween 80 are complex mixtures of components containing polyoxyethylene (POE) sorbitan and POE sorbitan monoesters ( Figure 10).…”

Section: Formulation Agentssupporting

confidence: 77%

“…Therefore, the composition of Tween 80 is quite variable and depends on the manufacturing process (Hewitt et al, 2011). Additionally, Tween 80 is rapidly hydrolyzed to oleic acid and polyethoxylated sorbitan by esterases in rodent plasma leading to further variability in analyses (Larger et al, 2005;van Tellingen et al, 1999). Dosing vehicles containing PEG 400 also lead to ionization suppression, in particular, for early eluting compounds (Shou and Naidong, 2003;Tong et al, 2002;Weaver and Riley, 2006;Xu et al, 2005).…”

Section: Formulation Agentsmentioning

confidence: 99%

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Identifying and Overcoming Matrix Effects in Drug Discovery and Development

Hall¹,

Smukste²,

Bresciano³

et al. 2012

Tandem Mass Spectrometry - Applications and Principles

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Section: Formulation Agentssupporting

confidence: 77%

Section: Formulation Agentsmentioning

confidence: 99%

Identifying and Overcoming Matrix Effects in Drug Discovery and Development

Hall¹,

Smukste²,

Bresciano³

et al. 2012

Tandem Mass Spectrometry - Applications and Principles

View full text Add to dashboard Cite

“…Recent studies highlighted the importance to prevent any alteration of the signal response induced by exogenous interfering compounds during method development (Souverain, Rudaz, & Veuthey, 2004;Larger et al, 2005;Weaver & Riley, 2006;Leverence et al, 2007). It has been demonstrated that polymers contained in different brands of plastic tubes and the anticoagulant Li-heparin can contribute to ME when analyzing plasma samples (Mei et al, 2003).…”

Section: A Bioanalytical and Pharmaceutical Analysismentioning

confidence: 99%

“…In pharmacokinetic studies, a major contribution to ME can be ascribed to the excipients often used as dosing vehicles (Tong et al, 2002;Shou & Weng, 2003;Larger et al, 2005;Weaver at al., 2006). Tween-80 and PEG400 are commonly employed in dosing formulations, via either intravenous or oral route, during the early drug discovery.…”

Section: A Bioanalytical and Pharmaceutical Analysismentioning

confidence: 99%

An overview of matrix effects in liquid chromatography–mass spectrometry

Trufelli

Palma

Famiglini

2010

Mass Spectrometry Reviews

641

433

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Matrix-dependent signal suppression or enhancement represents a major drawback in quantitative analysis with liquid chromatography coupled to atmospheric pressure ionization mass spectrometry (LC-API-MS). Because matrix effects (ME) might exert a detrimental impact on important method parameters (limit of detection, limit of quantification, linearity, accuracy, and precision), they have to be tested and evaluated during validation procedure. This review gives a detailed description on when these phenomena might be expected, and how they can be evaluated. The major sources of ME are discussed and illustrated with examples from bioanalytical, pharmaceutical, environmental, and food analysis. Because there is no universal solution for ME, the main strategies to overcome these phenomena are described in detail. Special emphasis is devoted to the sample-preparation procedures as well as to the recent improvements on chromatographic and mass spectrometric conditions. An overview of the main calibration techniques to compensate for ME is also presented. All these solutions can be used alone or in combination to retrieve the performance of the LC-MS for a particular matrix-analyte combination.

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“…Liquid chromatography-tandem mass spectrometry (LC-MS/MS) in which low molecular weight analytes (<2 kD) are separated from each other and from the endogenous components by liquid chromatography and then detected by tandem mass spectrometry has been the technique of choice for the past two decades (1)(2)(3)(4)(5)(6). One of the important considerations during mass spectrometric detection is the presence of matrix effect, in which ionization of the analytes of interest can be affected by the presence of co-eluting interfering components present in the sample matrix (7)(8)(9)(10)(11)(12). Matrix effect, in the form of ion suppression, or in some cases, ion enhancement, is a well-recognized phenomenon that affects bioanalysis by LC-MS/MS.…”

Section: Introductionmentioning

confidence: 99%

Utilizing Internal Standard Responses to Assess Risk on Reporting Bioanalytical Results from Hemolyzed Samples

Fung

Aubry

Allentoff

et al. 2015

AAPS J

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Abstract. Bioanalytical analysis of toxicokinetic and pharmacokinetic samples is an integral part of small molecule drugs development and liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been the technique of choice. One important consideration is the matrix effect, in which ionization of the analytes of interest is affected by the presence of co-eluting interfering components present in the sample matrix. Hemolysis, which results in additional endogenous components being released from the lysed red blood cells, may cause additional matrix interferences. The effects of the degree of hemolysis on the accuracy and precision of the method and the reported sample concentrations from hemolyzed study samples have drawn increasing attention in recent years, especially in cases where the sample concentrations are critical for pharmacokinetic calculation. Currently, there is no established procedure to objectively assess the risk of reporting potentially inaccurate bioanalytical results from hemolyzed study samples. In this work, we evaluated the effect of different degrees of hemolysis on the internal standard peak area, accuracy, and precision of the analyses of BMS-906024 and its metabolite, BMS-911557, in human plasma by LC-MS/MS. In addition, we proposed the strategy of using the peak area of the stable isotope-labeled internal standard (SIL-IS) from the LC-MS/MS measurement as the surrogate marker for risk assessment. Samples with peak areas outside of the pre-defined acceptance criteria, e.g., less than 50% or more than 150% of the average IS response in study samples, plasma standards, and QC samples when SIL-IS is used, are flagged out for further investigation.KEY WORDS: hemolyzed sample/haemolyzed sample; hyperlipemic sample; internal standard peak area/internal standard responses; LC-MS/MS; regulated bioanalysis; risk assessment.

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Ion-suppression effects in liquid chromatography–tandem mass spectrometry due to a formulation agent, a case study in drug discovery bioanalysis

Cited by 80 publications

References 19 publications

Identifying and Overcoming Matrix Effects in Drug Discovery and Development

Identifying and Overcoming Matrix Effects in Drug Discovery and Development

An overview of matrix effects in liquid chromatography–mass spectrometry

Utilizing Internal Standard Responses to Assess Risk on Reporting Bioanalytical Results from Hemolyzed Samples

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