Proteomic identification of biomarkers in maternal plasma that predict the outcome of rescue cerclage for cervical insufficiency

Objective We sought to identify plasma protein biomarkers that are predictive of the outcome of rescue cerclage in patients with cervical insufficiency. Methods This retrospective cohort study included 39 singleton pregnant women undergoing rescue cerclage for cervical insufficiency (17–25 weeks) who gave plasma samples. Three sets of pooled plasma samples from controls (cerclage success, n = 10) and cases (cerclage failure, n = 10, defined as spontaneous preterm delivery at <33 weeks) were labeled with 6-plex tandem mass tag (TMT) reagents and analyzed by liquid chromatography-tandem mass spectrometry. Differentially expressed proteins between the two groups were selected from the TMT-based quantitative analysis. Multiple reaction monitoring-mass spectrometry (MRM-MS) analysis was further used to verify the candidate proteins of interest in patients with cervical insufficiency in the final cohort (n = 39). Results From MRM-MS analysis of the 40 proteins showing statistically significant changes (P < 0.05) from the TMT-based quantitative analysis, plasma IGFBP-2, PSG4, and PGLYRP2 levels were found to be significantly increased, whereas plasma MET and LXN levels were significantly decreased in women with cerclage failure. Of these, IGFBP-2, PSG4, and LXN levels in plasma were independent of cervical dilatation. A multiple-biomarker panel was developed for the prediction of cerclage failure, using a stepwise regression procedure, which included the plasma IGFBP-2, PSG4, and LXN (area under the curve [AUC] = 0.916). The AUC for this multiple-biomarker panel was significantly greater than the AUC for any single biomarker included in the multi-biomarker model. Conclusions Proteomic analysis identified useful and independent plasma biomarkers (IGFBP-2, PSG4, and LXN; verified by MRM) that predict poor pregnancy outcome following rescue cerclage. Their combined analysis in a multi-biomarker panel significantly improved predictability.

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Simultaneous quantitative analysis of the antimalarials pyrimethamine and sulfamethoxypyrazine in plasma samples using liquid chromatography/tandem mass spectrometry

Rapid Communications in Mass Spectrometry ◽

10.1002/rcm.2670 ◽

2006 ◽

Vol 20 (19) ◽

pp. 2947-2953 ◽

Cited By ~ 8

Author(s):

Michael L. Storme ◽

F. Herwig Jansen ◽

Wim Goeteyn ◽

Jan F. Van Bocxlaer

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Quantitative Analysis ◽

Tandem Mass Spectrometry ◽

Tandem Mass ◽

Plasma Samples ◽

Chromatography Tandem Mass Spectrometry ◽

Liquid Chromatography Tandem Mass

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SIMULTANEOUS ESTIMATION OF PROPAFENONE AND ITS TWO METABOLITES IN HUMAN PLASMA BY LIQUID CHROMATOGRAPHY/TANDEM MASS SPECTROMETRY LC-MS/MS

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i8.18978 ◽

2017 ◽

Vol 9 (8) ◽

pp. 192

Author(s):

Rajeev Kumar Gupta ◽

Anand Chaurasia ◽

Brijeshkunvar Mishra

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Human Plasma ◽

Dynamic Range ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Simultaneous Estimation ◽

Tandem Mass ◽

Plasma Samples

Objective: A simple, sensitive and rapid performance liquid chromatography/positive ion electrospray tandem mass spectrometry method was to be developed and validated for quantification of propafenone (PPF) and its two major metabolite 5-hydroxy propafenone (5-OHP) and N-depropyl propafenone (NDP) in human plasma.Methods: Liquid-liquid extraction (LLE) with ethyl acetate was used of extraction of plasma samples. The analytes were separated using an isocratic mixture of 0.1% formic acid/acetonitrile (20:80 v/v) on a reversed-phase column Hypurity Advance C18 50 x2.1 mm, 5µ and analysed by mass spectrometry in the multiple reaction monitoring mode using the respective [M+H] Ions. The m/z was 342.20/116.10 for propafenone, m/z 299.80/74.10 for N depropyl propafenone and m/z 358.30/98.10 for 5-hydroxy propfenone along with m/z 409.2/238.0 for Amlodipine as internal standard respectively.Results: The method had a short chromatographic run time of 1.5 min. The method exhibited a linear dynamic range over 5.11 to 1000.73 ng/ml for propafenone, 0.51 to 100.06 ng/ml for N-depropyl propafenone and 5.11 to 1001.64 ng/ml for 5-hydroxy propafenone respectively, in human plasma.Conclusion: The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetics, bioavailability and bioequivalence studies.

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Determination of Chlorpromazine, Haloperidol, Levomepromazine, Olanzapine, Risperidone, and Sulpiride in Human Plasma by Liquid Chromatography/Tandem Mass Spectrometry (LC-MS/MS)

International Journal of Analytical Chemistry ◽

10.1155/2018/5807218 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 15

Author(s):

Abderrezak Khelfi ◽

Mohammed Azzouz ◽

Rania Abtroun ◽

Mohammed Reggabi ◽

Berkahoum Alamir

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

High Performance ◽

Solid Phase ◽

Multiple Reaction Monitoring ◽

Reversed Phase ◽

Tandem Mass ◽

Plasma Samples

Background and Objective. In this study, turbo-ion spray as an interface of tandem mass spectrometry (MS/MS) was performed for sensitive and accurate quantification of chlorpromazine, haloperidol, levomepromazine, olanzapine, risperidone, and sulpiride in plasma samples. Methods. Separation was performed by gradient reversed phase high-performance liquid chromatography using a mobile phase containing ammonium formiate 2 mM, pH 2.7, and acetonitrile flowing through a Restek PFP Propyl C18 analytical column (50 mm×2.1 mm i.d.) with particle size of 5 µm, at a flow rate of 800 µL/min. Positive ion fragments were detected in multiple reaction monitoring (MRM) mode. Sample preparation was achieved by solid phase extraction (SPE) (Oasis HLB). Results. Mean extraction recoveries ranged from 82.75% to 100.96%. The standard calibration curves showed an excellent linearity, covering subtherapeutic, therapeutic, and toxic ranges. Intraday and interday validation using quality control (QC) samples were performed. The inaccuracy and imprecision were below 12% at all concentration levels. The limits of detection (LOD) and quantification (LOQ) for all analytes were under therapeutic ranges for all tested analytes. Thus, the proposed method was sensitive enough for the detection and determination of subtherapeutic levels of these antipsychotics in plasma samples. No interference of endogenous or exogenous molecules was observed and no carryover effects were recorded. Conclusion. According to the results, the proposed method is simple, specific, linear, accurate, and precise and can be applied for antipsychotic analysis in clinical routine. This method was applied for the determination of the tested antipsychotics in plasma samples taken from 71 individuals.

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Development and Validation of Liquid Chromatography-Tandem Mass Spectrometry Method for Pharmacokinetic Evaluation of 7β-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranon in Rats

Molecules ◽

10.3390/molecules25081774 ◽

2020 ◽

Vol 25 (8) ◽

pp. 1774

Author(s):

Nae-Won Kang ◽

Jae-Young Lee ◽

Kwangho Song ◽

Min-Hwan Kim ◽

Soyeon Yoon ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Multiple Reaction Monitoring ◽

Acetonitrile Solution ◽

Tandem Mass ◽

Plasma Samples ◽

Chromatography Tandem Mass Spectrometry ◽

Relative Standard ◽

Liquid Chromatography Tandem Mass

Recently, potent neuroprotective and anti-diabetic effects of 7β-(3-Ethyl-cis-crotonoyloxy)-1α-(2-methylbutyryloxy)-3,14-dehydro-Z-notonipetranone (ECN), a sesquiterpenoid isolated from Tussilago farfara Linnaeus, have been elucidated. To facilitate further pre-clinical evaluation in rats, an analytical method for the determination of ECN in rat plasma was developed and optimized by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Plasma samples were pretreated by the protein precipitation method with an acetonitrile solution of losartan (LST) as the internal standard. Chromatographic separation was performed using a an Octadecyl-silica (ODS) column (2.6 µm, 100 x 4.6 mm) in the isocratic mode. The mobile phase, comprising 10 mM ammonium formate in water pH 5.75) and acetonitrile (11:89, v/v), was eluted at a flow rate of 0.4 mL/min. Mass spectrometric detection was performed in the multiple reaction monitoring mode with positive electrospray ionization, and the mass transitions of ECN and LST were m/z 431.3 to 97.3 and m/z 423.1 to 207.2, respectively. The calibration curves of spiked plasma samples were linear in the 10.0–10,000 ng/mL range (r2 > 0.996). The lower limit of quantification (LLOQ) was determined as 10.0 ng/mL. Validation was conducted in the LLOQ, and three quality control (QC) sample levels (10.0, 25.0, 3750, and 7500 ng/mL) were studied. Among them, the relative standard deviation for the within- and between-run precisions was under 9.90%, and the relative error of the accuracies was within the −8.13% to 0.42% range. The validated method was successfully employed to investigate the pharmacokinetic properties of ECN in rats, which revealed the linear pharmacokinetic behavior of ECN for the first time.

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A Novel Simultaneous Estimation of Sofosbuvir and Velpatasvir in Human Plasma by Liquid Chromatography Tandem-Mass Spectrometry after Protein Precipitation Method

Current Pharmaceutical Analysis ◽

10.2174/1573412914666180910102353 ◽

2019 ◽

Vol 15 (7) ◽

pp. 710-715

Author(s):

S.T. Narenderan ◽

Basuvan Babu ◽

T. Gokul ◽

Subramania Nainar Meyyanathan

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Human Plasma ◽

Multiple Reaction Monitoring ◽

Simultaneous Estimation ◽

Pharmacokinetic Studies ◽

Tandem Mass ◽

Mass Spectrometric Method ◽

Highly Sensitive ◽

Tandem Mass Spectrometric

Objective: The aim of the present work is to achieve a novel highly sensitive chromatographic method for the simultaneous determination of hepatitis C agents, sofosbuvir and velpatasvir from human plasma using ritonavir as an internal standard. Methods: Chromatographic separation was achieved using Hypersil C18 column (50mm x 4.6mm, 3μm) with an isocratic elution mode using the mobile phase composition 10 mM ammonium formate buffer (pH 5.0): acetonitrile (20:80 v/v) pumped at a flow rate of 0.5 ml/min. The detection was carried out by tandem mass spectrometry using Multiple Reaction Monitoring (MRM) positive Electrospray Ionization (ESI) with proton adducts at m/z 530.10 > 243.10, 883.40 > 114.0 and 721.25 > 197.0. Results: The method validated as per USFDA guidelines with respect to linearity, accuracy, and precision was found to be acceptable over the concentration range of 0.2–2000 ng/ml and 5-2000 ng/ml for sofosbuvir and velpatasvir respectively and the method was found to be highly sensitive and selective. Conclusion: The developed tandem mass spectrometric method is robust and can be applied for the monitoring of plasma levels of the analyzed drug in preclinical and clinical pharmacokinetic studies.

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Quantitative Analysis of Pyrazines and Their Perceptual Interactions in Soy Sauce Aroma Type Baijiu

Foods ◽

10.3390/foods10020441 ◽

2021 ◽

Vol 10 (2) ◽

pp. 441

Author(s):

Yan Yan ◽

Shuang Chen ◽

Yao Nie ◽

Yan Xu

Keyword(s):

Mass Spectrometry ◽

Quantitative Analysis ◽

Ultra Performance Liquid Chromatography ◽

Alcohol Solution ◽

Soy Sauce ◽

Tandem Mass ◽

Odor Thresholds ◽

Quantitative Results ◽

Odor Activity Value ◽

The Impact

Pyrazines are important compounds in soy sauce aroma type Baijiu (SSAB). In this work, a total of 16 pyrazines were analyzed using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC–MS/MS) in SSAB. The quantitative results showed that 2,3,5,6-tetramethylpyrazine, 2,6-dimethylpyrazine and 2,3,5-trimethylpyrazine were the three most concentrated pyrazines. The highest odor activity value (OAV) was determined for 2-ethyl-3,5-dimethylpyrazine. Quantitative analysis combined with descriptive sensory analysis revealed that sub-threshold pyrazines (2,3-dimethylpyrazine, 2,3-diethylpyrazine, 2,3-diethyl-5-methylpyrazine and 2-acetyl-3-methylpyrazine) are significantly correlated with the roasted aroma in SSAB. Our study focused on the impact of sub-threshold pyrazines on the perception of roasted aroma in SSAB. The effect of the sub-threshold pyrazines was detected by the addition of various pyrazines in SSAB samples, despite their sub-threshold concentrations. Furthermore, the presence of sub-threshold pyrazines in dilute alcohol solution resulted in a significant reduction in the odor thresholds of supra-threshold pyrazines. Sensory investigation indicated that pyrazines have a synergistic effect on the perception of roasted aroma. The results highlighted the contribution of some pyrazines to the roasted aroma in SSAB despite their sub-threshold concentrations.

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