scholarly journals Ultrahigh-Throughput ESI-MS: Sampling Pushed to Six Samples per Second by Acoustic Ejection Mass Spectrometry

2020 ◽  
Author(s):  
Tim Häbe ◽  
Chang Liu ◽  
Tom Covey ◽  
Roman P. Simon ◽  
Wolfgang Reindl ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Enzyme Assay ◽  
Sampling Rate ◽  
Internal Standard ◽  
Stress Tests ◽  
Esi Ms ◽  
Droplet Ejection ◽  
Signal Suppression ◽  
Dog Plasma ◽  
Open Port

<div> <p> We present an acoustic ejection mass spectrometry (AEMS) setup for ESI-MS based sample </p><p> injection at a sampling rate faster than current ESI and MALDI techniques. A modified acoustic </p><p> droplet ejection system was combined with an open port interface and a modified ESI source. To </p><p> simulate applications of drug metabolism and pharmacokinetics analysis and high-throughput </p><p> screening campaigns, two stress tests were performed regarding ion suppression and system </p><p> endurance in combination with minor sample preparation. Maximum sampling rate was 6 Hz for </p><p> dextromethorphan and d3-dextrorphan (each 100 nM) for 1152 injections in 63 s at FWHM of </p><p> 105 ms and %RSD of 7.7%/7.5% without internal standard correction. Enzyme assay buffer and </p><p> crude dog plasma caused signal suppression of 51%/73% at %RSD of 5.7%/6.7% (n = 120) and </p><p> stable OPI performance during 1100 injections. An endurance buffer revealed minor OPI pollution </p><p> and constant signals for >25.000 injections (%RSD = 8.5%, n = 10,557). </p></div>

scholarly journals Ultrahigh-Throughput ESI-MS: Sampling Pushed to Six Samples per Second by Acoustic Ejection Mass Spectrometry

2020 ◽  
Author(s):  
Tim Häbe ◽  
Chang Liu ◽  
Tom Covey ◽  
Roman P. Simon ◽  
Wolfgang Reindl ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Enzyme Assay ◽  
Sampling Rate ◽  
Internal Standard ◽  
Stress Tests ◽  
Esi Ms ◽  
Droplet Ejection ◽  
Signal Suppression ◽  
Dog Plasma ◽  
Open Port

<div> <p> We present an acoustic ejection mass spectrometry (AEMS) setup for ESI-MS based sample </p><p> injection at a sampling rate faster than current ESI and MALDI techniques. A modified acoustic </p><p> droplet ejection system was combined with an open port interface and a modified ESI source. To </p><p> simulate applications of drug metabolism and pharmacokinetics analysis and high-throughput </p><p> screening campaigns, two stress tests were performed regarding ion suppression and system </p><p> endurance in combination with minor sample preparation. Maximum sampling rate was 6 Hz for </p><p> dextromethorphan and d3-dextrorphan (each 100 nM) for 1152 injections in 63 s at FWHM of </p><p> 105 ms and %RSD of 7.7%/7.5% without internal standard correction. Enzyme assay buffer and </p><p> crude dog plasma caused signal suppression of 51%/73% at %RSD of 5.7%/6.7% (n = 120) and </p><p> stable OPI performance during 1100 injections. An endurance buffer revealed minor OPI pollution </p><p> and constant signals for >25.000 injections (%RSD = 8.5%, n = 10,557). </p></div>

scholarly journals Pressurized Solvent Extraction with Ethyl Acetate and Liquid Chromatography—Tandem Mass Spectrometry for the Analysis of Selected Conazole Fungicides in Matcha

Toxics ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 64 ◽  
Author(s):  
Renata Raina-Fulton ◽  
Aisha Mohamad
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Solvent Extraction ◽  
Matrix Effects ◽  
Tandem Mass ◽  
Esi Ms ◽  
Signal Suppression ◽  
Target Analytes ◽  
Matrix Components ◽  
Pressurized Solvent Extraction

The extraction of powdered nutraceuticals is challenging due to the low water content and high concentration of matrix components that can lead to significant matrix effects in liquid chromatography-positive ion electrospray ionization-tandem mass spectrometry (LC-ESI+-MS/MS). In this study we assess the feasibility of using pressurized solvent extraction with ethyl acetate to reduce the co-extraction of polar matrix components. Pigment attributed to chlorophyll was removed with in-cell clean-up utilizing Anasorb 747, Florisil®, and C18. Visible inspection of the extracts showed that pigment was removed from matcha, a powdered green tea sample. Pressurized solvent extraction with in-cell clean-up can be utilized to remove pigments from powdered samples such as nutraceuticals. Average matrix effect of the 32 target analytes that observed mass spectrometric signal suppression or soft MS signal enhancement was −41 ± 19% with the majority of analytes having a protonated molecular ion with m/z of 250 to 412. As generally moderate signal suppression was observed for conazole fungicides and structurally related compounds analyzed by LC-ESI+-MS/MS, it is recommended that matrix matched or standard addition calibration is used for quantitation. Catachins, other polyphenols, and caffeine are expected to contribute to the matrix effects observed in LC-ESI+-MS/MS. Diniconazole, fenbuconazole, and tebufenozide were the only target analytes with severe MS signal enhancement. Low levels (0.002–0.004 mg/kg) of prothioconazole-desthio and flusilazole were detected, along with trace levels of tebuthiuron in matcha.

scholarly journals Simultaneous Determination of Levocetirizine and Pseudoephedrine in Dog Plasma by Liquid Chromatography-Mass Spectrometry in the Presence of Dextrocetirizine

2012 ◽  
Vol 15 (4) ◽  
pp. 519 ◽  
Author(s):  
Jae Kuk Ryu ◽  
Sun Dong Yoo
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Oral Administration ◽  
Mobile Phase ◽  
Internal Standard ◽  
Liquid Chromatography Mass Spectrometry ◽  
Chiral Column ◽  
Accuracy And Precision ◽  
Dog Plasma

Purpose. This study describes the development of a rapid and sensitive LC-ESI-MS assay for simultaneous enantioselective determination of levocetirizine and pseudoephedrine in dog plasma in the presence of dextrocetirizine. Methods. Separations were achieved on an Ultron ES-OVM chiral column using the mobile phase consisting of 10 mM aqueous NH4OAc (pH 6.6) and acetonitrile (9:1 v/v). Results. The retention times of pseudoephedrine, dextrocetirizine, levocetirizine and diazepam (internal standard) were 5.2, 8.3, 9.6 and 11.6 min, respectively, and the total run time was less than 15 min. The assay was validated to demonstrate the linearity, accuracy and precision, recovery and stability. The calibration curves were linear over the concentration range from 1 – 200 ng/mL for levocetirizine and from 5 – 1000 ng/mL for pseudoephedrine. Conclusions. The developed assay was successfully applied to a pharmacokinetic study after oral administration of the racemic cetirizine (0.5 mg/kg, or 0.25 mg/kg as levocetirizine) and pseudoephedrine (12 mg/kg) in the dog. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Ultra-High-Throughput Acoustic Droplet Ejection-Open Port Interface-Mass Spectrometry for Parallel Medicinal Chemistry

2020 ◽  
Vol 11 (6) ◽  
pp. 1101-1110 ◽  
Author(s):  
Kenneth J. DiRico ◽  
Wenyi Hua ◽  
Chang Liu ◽  
Joseph W. Tucker ◽  
Anokha S. Ratnayake ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Throughput ◽  
Medicinal Chemistry ◽  
Droplet Ejection ◽  
Open Port

Internal standard signal suppression by co-eluting analyte in isotope dilution LC-ESI-MS

The Analyst ◽  
2002 ◽  
Vol 128 (1) ◽  
pp. 51-54 ◽  
Author(s):  
Luis E. Sojo ◽  
Gina Lum ◽  
Priscilla Chee
Keyword(s):  
Isotope Dilution ◽  
Internal Standard ◽  
Esi Ms ◽  
Standard Signal ◽  
Signal Suppression

scholarly journals Evaluation of a Deuterium-Labeled Internal Standard for the Measurement of Sirolimus by High-Throughput HPLC Electrospray Ionization Tandem Mass Spectrometry

2008 ◽  
Vol 54 (8) ◽  
pp. 1386-1389 ◽  
Author(s):  
Sean O'Halloran ◽  
Kenneth F Ilett
Keyword(s):  
Mass Spectrometry ◽  
Tandem Mass Spectrometry ◽  
Electrospray Ionization ◽  
High Throughput ◽  
Matrix Effects ◽  
Internal Standard ◽  
Tandem Mass ◽  
Esi Ms ◽  
Interpatient Variation ◽  
Ionization Tandem Mass Spectrometry

Abstract Background: Matrix effects in HPLC–electrospray ionization–tandem mass spectrometry (HPLC-ESI-MS/MS)1 can cause differences in the ionization of an internal standard (IS) compared with the analyte of interest. Unless sample cleanup or chromatographic conditions eliminate or minimize ion suppression or enhancement, variability in interpatient matrices may cause erroneous results. A stable isotope-labeled IS can be used to minimize analytical interpatient variation. Methods: We used protein precipitation and HPLC-ESI-MS/MS to quantify sirolimus (SIR) with both desmethoxyrapamycin (DMR) and deuterium-labeled sirolimus (SIR-d3) as the IS to analyze a range of whole-blood and extraction-matrix samples, and to estimate recovery, matrix effects, process efficiency, and interpatient variation. We also analyzed a series of blood samples from 72 patients taking SIR, including external proficiency-testing samples, with these ISs. Results: The range of interpatient assay imprecision (CV) values for the SIR assay was consistently lower with SIR-d3 (2.7%–5.7%) than with DMR (7.6%–9.7%). The results obtained with the 2 different ISs for the patient samples showed a linear relationship, but the results were higher with DMR as the IS than with SIR-d3. Conclusions: The use of SIR-d3 as the IS in the high-throughput HPLC-ESI-MS/MS assay of SIR yielded improved results compared with the use of DMR. SIR-d3 appears to be less affected by differences in the ionization of SIR and its IS caused by the variability of interpatient matrices. The IS-related difference in SIR estimation needs further investigation.

Revealing changes in curcumin bioavailability using vitamin C as an enhancer by HPLC-MS/MS

2019 ◽  
Vol 16 ◽  
Author(s):  
Xufen Dai ◽  
Jiaxue Hao ◽  
Ying Feng ◽  
Jing Wang ◽  
Qiannan Li ◽  
...  
Keyword(s):  
Vitamin C ◽  
High Performance ◽  
Internal Standard ◽  
Fold Increase ◽  
Rat Plasma ◽  
Pharmacokinetic Parameters ◽  
Solution Ph ◽  
Esi Ms ◽  
Simple Strategy ◽  
Isolated Compound

Background: Curcumin (CUR), a natural isolated compound from turmeric, has been the promising star in fighting many diseases but the broad application of curcumin has been limited ascribed to low bioavailability. Objective: The aim of this study is to pursue the enhancement of curcumin bioavailability through co-administration of vitamin C. Methods: Such purpose was achieved through the analysis of curcumin pharmacokinetics by high performance liquid chromatography coupled with electrospray ionization - tandem mass spectrometry (HPLC - ESI - MS/MS). The plasma was separated on a C18 reverse phase column using acetonitrile and ammonium formate solution (pH 6.5; 2.0 mM) at 0.8 mL/min. MS/MS detection was carried out in negative mode using mass patterns of m/z 367.0 > 216.7 for curcumin and m/z 265.2 > 223.9 for internal standard (honokiol). Results: Successful application of the proposed method in the pharmacokinetic study presented clear changes in key pharmacokinetic parameters including the growth of AUC (0-t) up to 2.4 times, 2.2-fold increase of Cmax, 2.2-fold loss of CL, and 1.5-fold diminishment of t1/2. Conclusion: We developed an HPLC-ESI-MS/MS method for determination of curcumin in rat plasma and validated the improvement of bioavailability of curcumin through co-administration of vitamin C. We reasoned these changes to the inhibition of lipid peroxidation induced by the use of vitamin C. Such a simple strategy is possible to become an alternative for enhancing curcumin efficiency in practice.

scholarly journals Analysis of Pembrolizumab in Human Plasma by LC-MS/HRMS. Method Validation and Comparison with Elisa

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 621
Author(s):  
Aurélien Millet ◽  
Nihel Khoudour ◽  
Jérôme Guitton ◽  
Dorothée Lebert ◽  
François Goldwasser ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Human Plasma ◽  
High Resolution Mass Spectrometry ◽  
Internal Standard ◽  
Therapeutic Drug ◽  
Limit Of Quantification ◽  
Immunoglobulin G4 ◽  
Positive Mode ◽  
Surrogate Peptide ◽  
First Time

Pembrolizumab is a humanized immunoglobulin G4-kappa anti-PD1 antibody used in the treatment of different solid tumors or haematological malignancies. A liquid chromatography coupled with a high resolution mass spectrometry (orbitrap technology) method was fully developed, optimized, and validated for quantitative analysis of pembrolizumab in human plasma. A mass spectrometry assay was used for the first time a full-length stable isotope-labelled pembrolizumab-like (Arginine 13C6-15N4 and Lysine 13C6-15N2) as an internal standard; the sample preparation was based on albumin depletion and trypsin digestion and, finally, one surrogate peptide was quantified in positive mode. The assay showed good linearity over the range of 1–100 μg/mL, a limit of quantification at 1 μg/mL, excellent accuracy from 4.4% to 5.1%, and also a between-day precision below 20% at the limit of quantification. In parallel, an in-house ELISA was developed with a linearity range from 2.5 to 50 µg/mL. Then, results were obtained from 70 plasma samples of cancer patients that were treated with pembrolizumab and quantified with both methods were compared using the Passing-Bablok regression analysis and Bland-Altman plotting. The LC-MS/HRMS method is easy to implement in the laboratory for use in the context of PK/PD studies, clinical trials, or therapeutic drug monitoring.

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