Determination of eptifibatide concentration in human plasma utilizing the liquid chromatography–tandem mass spectrometry method

Liu, Jia; Duan, Xiaotao; Chen, Xiaoyan; Zhong, Dafang

doi:10.1016/j.jchromb.2008.12.060

Cited by 11 publications

(11 citation statements)

References 8 publications

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“…In this report, we studied the ETD fragmentation of the model cyclic peptide eptifibatide, which is a potent antagonist for glycoprotein IIb/IIIa and has been widely used in clinical practices to inhibit platelet aggregation [11]. Our study demonstrated CID of this disulfide-containing cyclic peptide failed to produce a sequence-informative fragmentation pattern, confirming the previous observations [11, 12].…”

supporting

confidence: 82%

Electron transfer dissociation coupled to an Orbitrap analyzer may promise a straightforward and accurate sequencing of disulfide‐bridged cyclic peptides: a case study

Duan

Engler

2010

J. Mass Spectrom.

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Dear Sir, Electron transfer dissociation coupled to an Orbitrap analyzer may promise a straightforward and accurate sequencing of disulfide-bridged cyclic peptides: a case study Cyclic peptides constitute a large group of compounds that possess potent biological and pharmacological activities, and thus have attracted ever-growing attentions in areas such as drug development and biomedical research [1]. Therefore, the ability to analyze cyclic peptides by high-throughput methods such as the tandem mass spectrometry (MS) will be of high interest [2]. Nevertheless, sequencing of these peptides by conventional MS techniques, which typically employ collision induced dissociation (CID) to obtain sequence-informative fragments, represents a daunting challenge. Cyclic peptides maintain a highly rigid conformation due to a circular backbone, which often accounts for their high receptor selectivity, metabolic stability, and potency [1]. Circular backbones present several challenges when sequencing by CID. First, the largely random initial ring scissions of the backbone often result in a perplexing mixture of different sets of b/y ions and neutral loss/ internal fragments [3], rendering the CID spectra very complex [2,4]. Second, the CID fragmentation of cyclic peptides often produces many fragments that are not typical for the cleavage of a linear peptide (such as sequence scrambling product ions), and thus are difficult to interpret [4,5]. Third, the cyclic backbone of a majority of therapeutic cyclic peptides is held together by a disulfide bond that cannot be cleaved efficiently utilizing the CID mechanism [6]. Consequently, the application of CID for the structure elucidation of cyclic peptides is severely limited.Electron transfer dissociation (ETD), which is an analogue of the electron capture dissociation (ECD) technique, converts multiple-charged peptide cations into radicals and cleaves the N-C α bonds, providing a fragmentation mechanism orthogonal to that by CID [7,8]. The resulting fragment ions that contain the N-and C-termini of the peptides are termed c and z ions, respectively. It has been demonstrated that the electron-initiated dissociation during an ETD process is less discriminated by the amino acid residues and side-chain chemistry compared with CID [7]. As a result, in most cases ETD provides more complete peptide backbone cleavage, and shows particular strength in the identification of [7,8]. Another advantage of ETD over CID is that it provides efficient cleavage of disulfide bonds (cf. the discussion), which may enable the localization of disulfide linkages in peptides or intact proteins under non-reducing conditions. Therefore, it is possible to utilize the ETD technique to achieve a favorable sequencing of the disulfide-bridged cyclic peptides, which account for most of the cyclic peptides.So far only a few studies have been conducted on the fragmentation of cyclic peptides by ETD or ECD [9,10]. As a result, a detailed investigation of the ETD behaviors of cyclic peptides, as well as an evaluat...

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supporting

confidence: 82%

Electron transfer dissociation coupled to an Orbitrap analyzer may promise a straightforward and accurate sequencing of disulfide‐bridged cyclic peptides: a case study

Duan

Engler

2010

J. Mass Spectrom.

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“…Under these conditions, the selectivity and sensitivity were improved greatly. The LLOQ of the method was 1 ng/mL which was lower than that reported in the previous method [5].…”

Section: Optimization Of the Mass Spectrometriccontrasting

confidence: 60%

“…In the study [5] related to analyzing the concentration of eptifibatide in human plasma, analytes and the IS were detected by tandem mass spectrometry using modified multiple reaction monitoring (MRM) of precursor-precursor ion transitions at m/z 832.6-832.6 for eptifibatide and m/z 931.3-931.3 for internal standard. However, the selectivity of tandem mass spectrometry was reduced when using this modified MRM process.…”

Section: Optimization Of the Mass Spectrometricmentioning

confidence: 99%

“…It is critical to develop a sensitive and selective method for the analysis of eptifibatide concentration in plasma so as to evaluate its pharmacokinetics [5]. Few methods have, however, been reported to quantify plasma concentrations of eptifibatide.…”

Section: Introductionmentioning

confidence: 99%

“…Few methods have, however, been reported to quantify plasma concentrations of eptifibatide. To the best of our knowledge only one liquid chromatography-tandem mass spectrometry (LC-MS/MS) method [5] with LLOQ of 4.61 ng/mL utilizing the modified MRM process and protein precipitation for sample preparation has been developed and validated for the measurement of eptifibatide concentrations in human plasma. This modified MRM process used the precursor-precursor ion transition of m/z 832.6 → m/z 832.6 and m/z 931.3 → m/z 931.3 to quantify eptifibatide and the IS, respectively.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Improved liquid chromatography–tandem mass spectrometry method for the analysis of eptifibatide in human plasma

Zhou

Xin

Yang

et al. 2010

Journal of Chromatography B

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Spectrofluorimetric determination of eptifibatide in human plasma and dosage form

et al. 2018

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A spectrofluorimetric method for the determination of eptifibatide is presented based on its native fluorescence. The type of solvent and the wavelength of maximum excitation and emission were carefully selected to optimize the experimental conditions. Under the specified experimental conditions, the linearities obtained between the emission intensity and the corresponding concentrations of eptifibatide were in the range 0.1–2.5 μg/ml for the calibration curve constructed for direct determination of eptifibatide in dosage form and 0.05–2.2 μg/ml for the calibration curve constructed in spiked human plasma with a good correlation coefficient (r > 0.99). The lower limit of quantification for the calibration curve constructed in human plasma was 0.05 μg/ml. Recovery results for eptifibatide in spiked plasma samples and in dosage form, represented as mean ± % RSD, were 95.17 ± 1.94 and 100.29 ± 1.33 respectively. The suggested procedures were validated according to the International Conference on Harmonization (ICH) guidelines for the direct determination of eptifibatide in its pure form and dosage form and United States Food and Drug Administration (US FDA) Guidance for Industry, Bioanalytical Method Validation for the assay of eptifibatide in human plasma.

show abstract

Determination of eptifibatide concentration in human plasma utilizing the liquid chromatography–tandem mass spectrometry method

Cited by 11 publications

References 8 publications

Electron transfer dissociation coupled to an Orbitrap analyzer may promise a straightforward and accurate sequencing of disulfide‐bridged cyclic peptides: a case study

Electron transfer dissociation coupled to an Orbitrap analyzer may promise a straightforward and accurate sequencing of disulfide‐bridged cyclic peptides: a case study

Improved liquid chromatography–tandem mass spectrometry method for the analysis of eptifibatide in human plasma

Spectrofluorimetric determination of eptifibatide in human plasma and dosage form

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