Simultaneous quantification of enalapril and enalaprilat in human plasma by high-performance liquid chromatography–tandem mass spectrometry and its application in a pharmacokinetic study

Lu, Shan; Jiang, Kun; Qin, Feng; Lu, Xiumei; Li, Famei

doi:10.1016/j.jpba.2008.10.012

Cited by 30 publications

(19 citation statements)

References 10 publications

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“…46,47 This LOQ compares favorably with values obtained via HPLC-UV (12 ng/mL) 48 but is roughly an order of magnitude higher than results reported using HPLC–MS. 49 In addition to an improvement in precision, improvements in enalapril linearity (Supplemental Figure 2) and accuracy (Table 2) were also observed upon normalization to ramipril. As determined in the range of 0.03 to 10 μ M, a least-squares linear regression analysis showed an improvement in the correlation coefficient from R 2 ≈ 0.9966 to R 2 ≈ 0.9998 upon normalization (Supplemental Figure 2).…”

Section: Resultsmentioning

confidence: 90%

Multiple Time-of-Flight/Time-of-Flight Events in a Single Laser Shot for Improved Matrix-Assisted Laser Desorption/Ionization Tandem Mass Spectrometry Quantification

et al. 2016

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Quantitative matrix-assisted laser desorption/ionization time-of-flight (MALDI TOF) approaches have historically suffered from poor accuracy and precision mainly due to the nonuniform distribution of matrix and analyte across the target surface, matrix interferences, and ionization suppression. Tandem mass spectrometry (MS/MS) can be used to ensure chemical specificity as well as improve signal-to-noise ratios by eliminating interferences from chemical noise, alleviating some concerns about dynamic range. However, conventional MALDI TOF/TOF modalities typically only scan for a single MS/MS event per laser shot, and multiplex assays require sequential analyses. We describe here new methodology that allows for multiple TOF/TOF fragmentation events to be performed in a single laser shot. This technology allows the reference of analyte intensity to that of the internal standard in each laser shot, even when the analyte and internal standard are quite disparate in m/z, thereby improving quantification while maintaining chemical specificity and duty cycle. In the quantitative analysis of the drug enalapril in pooled human plasma with ramipril as an internal standard, a greater than 4-fold improvement in relative standard deviation (<10%) was observed as well as improved coefficients of determination (R2) and accuracy (>85% quality controls). Using this approach we have also performed simultaneous quantitative analysis of three drugs (promethazine, enalapril, and verapamil) using deuterated analogues of these drugs as internal standards.

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Section: Resultsmentioning

confidence: 90%

Multiple Time-of-Flight/Time-of-Flight Events in a Single Laser Shot for Improved Matrix-Assisted Laser Desorption/Ionization Tandem Mass Spectrometry Quantification

et al. 2016

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“…Compared to other MS approaches, MRM provides higher sensitivity and specificity 28 . MRM assays have been used to study the pharmacokinetics of enalapril, an ACE inhibitor used in the treatment of hypertension and congestive heart failure 51 . The MRM approach was also used to simultaneously quantify seven angiotensin II receptor antagonists in plasma of patients undergoing cardiovascular treatment 52 .…”

Section: How To Develop a Quantitative View Of Proteolytic Processing?mentioning

confidence: 99%

Targeting Proteases in Cardiovascular Diseases by Mass Spectrometry-Based Proteomics

Klingler

Hardt

2012

Circ Cardiovasc Genet

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Proteases hydrolyze peptide bonds, thereby controlling the function of proteins and peptides on the posttranslational level. In the cardiovascular system, proteases play pivotal roles in the regulation of blood pressure, coagulation and other essential physiological processes. Accordingly, proteases are prime targets for therapeutic interventions and diagnostics. Proteases are part of complex proteolytic networks comprised of enzymes, inhibitors, activators, substrates and cleavage products. Analyzing these networks on a system-wide level is essential to understanding cardiovascular function and how dysregulation can lead to pathological conditions. Mass spectrometry-based quantitative and dynamic proteomics approaches are leading the way to enhance our knowledge of proteolytic networks such as the renin-angiotensin-system. Here, we critically review proteomics tools utilized in protease biology and provide an overview on how these methods can be used to characterize and validate protease function.

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“…So far little of the potential that MRM assays could have in protease research has been realized. Notable exceptions are the utilization of MRM-assays to measure the abundances of vasoactive peptides in plasma in response to the injection of ACE-inhibitors [54] and the absolute quantitation of protease inhibitors in patient samples [55]. …”

Section: Introductionmentioning

confidence: 99%

Profiling protease activities by dynamic proteomics workflows

Klingler

Hardt

2012

Proteomics

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Proteases play prominent roles in many physiological processes and the pathogenesis of various diseases, which makes them interesting drug targets. To fully understand the functional role of proteases in these processes, it is necessary to characterize the target specificity of the enzymes, identify endogenous substrates and cleavage products as well as protease activators and inhibitors. The complexity of these proteolytic networks presents a considerable analytic challenge. To comprehensively characterize these systems, quantitative methods that capture the spatial and temporal distributions of the network members are needed. Recently, activity-based workflows have come to the forefront to tackle the dynamic aspects of proteolytic processing networks in vitro, ex vivo and in vivo. In this review, we will discuss how mass spectrometry-based approaches can be used to gain new insights into protease biology by determining substrate specificities, profiling the activity-states of proteases, monitoring proteolysis in vivo, measuring reaction kinetics and defining in vitro and in vivo proteolytic events. In addition, examples of future aspects of protease research that go beyond mass spectrometry-based applications are given.

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Simultaneous quantification of enalapril and enalaprilat in human plasma by high-performance liquid chromatography–tandem mass spectrometry and its application in a pharmacokinetic study

Cited by 30 publications

References 10 publications

Multiple Time-of-Flight/Time-of-Flight Events in a Single Laser Shot for Improved Matrix-Assisted Laser Desorption/Ionization Tandem Mass Spectrometry Quantification

Multiple Time-of-Flight/Time-of-Flight Events in a Single Laser Shot for Improved Matrix-Assisted Laser Desorption/Ionization Tandem Mass Spectrometry Quantification

Targeting Proteases in Cardiovascular Diseases by Mass Spectrometry-Based Proteomics

Profiling protease activities by dynamic proteomics workflows

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