scholarly journals Separation and Quantification of Superwarfarin Rodenticide Diastereomers—Bromadiolone, Difenacoum, Flocoumafen, Brodifacoum, and Difethialone—in Human Plasma

2020 ◽  
Vol 103 (3) ◽  
pp. 770-778
Author(s):  
Daniel G Nosal ◽  
Douglas L Feinstein ◽  
Luying Chen ◽  
Richard B van Breemen
Keyword(s):  
Human Plasma ◽  
Clinical Care ◽  
Reversed Phase ◽  
Negative Ion ◽  
Ultrahigh Pressure ◽  
Selected Reaction Monitoring ◽  
Triple Quadrupole Mass Spectrometer ◽  
Accuracy And Precision ◽  
Liquid Chromatography Tandem Mass ◽  
Long Acting

Abstract Background Superwarfarins, second-generation long-acting anticoagulant rodenticides, are 4-hydroxycoumarin analogues of warfarin that contain a large hydrophobic side chain. These compounds contain two chiral centers and are synthesized for commercial use as two pairs of diastereomer. Objective To support studies of superwarfarin pharmacokinetics and other efforts to improve clinical care for poisoning victims, a quantitative assay was developed for the measurement of diastereomer of bromadiolone, difenacoum, flocoumafen, brodifacoum, and difethialone in human plasma. Method Based on ultrahigh-pressure liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS), this method was validated according to U.S. Food and Drug Administration (FDA) guidelines. Sample preparation involved simple protein precipitation followed by reversed phase UHPLC, which resolved all five pairs of cis/trans diastereomer in less than 10 min. Superwarfarins were measured using negative ion electrospray followed by selected-reaction monitoring on a triple quadrupole mass spectrometer. Results Calibration curves covered 3–4 orders of magnitude with linear regression coefficients of >0.999. The lower limits of quantitation were from 0.013 to 2.41 ng/mL, and intra-day and inter-day accuracy and precision coefficients of variation were <12%. Conclusions A 10-min UHPLC-MS/MS assay was developed and validated for the separation and quantitative analysis of the pairs of diastereomer of five superwarfarins in human plasma. Highlights This method was used to identify and measure superwarfarins and their cis/trans diastereomers in plasma obtained from patients treated for coagulopathy following consumption of contaminated synthetic cannabinoid products.

scholarly journals Development and validation of a liquid chromatography-tandem mass spectrometric method for the determination of lenalidomide in human plasma and its application on bioequivalence studies

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
R. Gopinath ◽  
S. T. Narenderan ◽  
M. Kumar ◽  
B. Babu
Keyword(s):  
Liquid Chromatography ◽  
Human Plasma ◽  
Internal Standard ◽  
Spectrometric Method ◽  
Tandem Mass ◽  
Mass Spectrometric Method ◽  
Mass Detection ◽  
Triple Quadrupole Mass Spectrometer ◽  
Liquid Chromatography Tandem Mass ◽  
Tandem Mass Spectrometric

AbstractA simple, sensitive, and specific liquid chromatography-tandem mass spectrophotometry (LC-MS/MS) method was developed and validated for the quantification of lenalidomide in human plasma. The separation was carried out on a symmetry, C18, 5-μm (50 × 4.6 mm) column as stationary phase and with an isocratic mobile phase of 0.1% formic acid in water-methanol in the ratio of (15:85, v/v) at a flow rate of 0.5 mL/min. Protonated ions formed by electrospray ionization in the positive mode were used to detect analyte and fluconazole (internal standard). The mass detection was made by monitoring the fragmentation of m/z 260.1/148.8 for lenalidomide and m/z 307.1/238.0 for internal standard on a triple quadrupole mass spectrometer. The developed method was validated over the concentration range of 10–1000 ng/mL for lenalidomide in human plasma with a correlation coefficient (r2) was 0.9930. The accuracy and precision values obtained from six different sets of quality control samples analyzed on separate occasions ranged from 99.41 to 106.97% and 2.88 to 4.22%, respectively. Mean extraction recoveries were 98.06% and 88.78% for the analyte and IS, respectively. The developed method was successfully applied for analyzing lenalidomide in human plasma samples.

scholarly journals Development and Validation of a LC–MS/MS-Based Assay for Quantification of Free and Total Omega 3 and 6 Fatty Acids from Human Plasma

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 360 ◽  
Author(s):  
Vlad Serafim ◽  
Diana-Andreea Tiugan ◽  
Nicoleta Andreescu ◽  
Alexandra Mihailescu ◽  
Corina Paul ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Human Plasma ◽  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Reversed Phase ◽  
Omega 3 ◽  
Mass Detection ◽  
Liquid Chromatography Tandem Mass ◽  
Negative Electrospray Ionization ◽  
Nanomolar Range

Few high-performance liquid chromatography–tandem mass spectrometry (LC-MS/MS) methods have been developed for the full quantitation of fatty acids from human plasma without derivatization. Therefore, we propose a method that requires fewer sample preparation steps, which can be used for the quantitation of several polyunsaturated fatty acids in human plasma. The method offers rapid, accurate, sensitive, and simultaneous quantification of omega 3 (α-linolenic, eicosapentaenoic, and docosahexaenoic acids) and omega 6 fatty acids (arachidonic and linoleic acids) using high-performance LC-MS/MS. The selected fatty acids were analysed in lipid extracts from both free and total forms. Chromatographic separation was achieved using a reversed phase C18 column with isocratic flow using ammonium acetate for improving negative electrospray ionization (ESI) response. Mass detection was performed in multiple reaction monitoring (MRM) mode, and deuterated internal standards were used for each target compound. The limits of quantification were situated in the low nanomolar range, excepting linoleic acid, for which the limit was in the high nanomolar range. The method was validated according to the U.S. Department of Health and Human Services guidelines, and offers a fast, sensitive, and reliable quantification of selected omega 3 and 6 fatty acids in human plasma.

scholarly journals Validation of Liquid Chromatography–Tandem Mass Spectrometry Method for Analysis of Urinary Conjugated Metanephrine and Normetanephrine for Screening of Pheochromocytoma

2002 ◽  
Vol 48 (3) ◽  
pp. 533-539 ◽  
Author(s):  
Robert L Taylor ◽  
Ravinder J Singh
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Solid Phase ◽  
Reversed Phase ◽  
Selected Reaction Monitoring ◽  
Gas Chromatography Mass Spectrometry ◽  
Tandem Mass ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

Abstract Background: Metanephrines are biochemical markers for tumors of the adrenal medulla (e.g., pheochromocytoma) and other tumors derived from neural crest cells (e.g., paragangliomas and neuroblastomas). We describe a liquid chromatography–tandem mass spectrometry (LC-MS/MS) method for the measurement of urinary conjugated metanephrines. Methods: We added 250 ng of d3-metanephrine (d3-MN) and 500 ng of d3-normetanephrine (d3-NMN) to 1 mL of urine samples as stable isotope internal standards. The samples were then acidified, hydrolyzed for 20 min in a 100 °C water bath, neutralized, and prepared by solid-phase extraction. The methanol eluates were analyzed by LC-MS/MS in the selected-reaction-monitoring mode after separation on a reversed-phase amide C16 column. Results: Multiple calibration curves for the analysis of urine MN and NMN exhibited consistent linearity and reproducibility in the range of 10–5000 μg/L. Interassay CVs were 5.7–8.6% at mean concentrations of 90–4854 μg/L for MN and NMN. The detection limit was 10 μg/L. Recovery of MN and NMN (144–2300 μg/L) added to urine was 91–114%. The regression equation for the LC-MS/MS (x) and colorimetric (y) methods was: y = 0.81x − 0.006 (r = 0.822; n = 110). The equation for the HPLC (x) and LC-MS/MS (y) methods was: y = 1.09x + 0.05 (r = 0.998; n = 40). Conclusions: The sensitivity and specificity of the MS/MS method for urinary conjugated metanephrines offer advantages over colorimetric, immunoassay, HPLC, and gas chromatography–mass spectrometry methods because of elimination of drug interferences, high throughput, and short chromatographic run time.

scholarly journals Reliable and Easy-To-Use Liquid Chromatography-Tandem Mass Spectrometry Assay for Quantification of Olorofim (F901318), a Novel Antifungal Drug, in Human Plasma and Serum

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Carsten Müller ◽  
Cornelia Fietz ◽  
Philipp Koehler ◽  
Graham Sibley ◽  
Achu Che Awah Nforbugwe ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Human Plasma ◽  
Antifungal Drug ◽  
Selected Reaction Monitoring ◽  
Tandem Mass ◽  
Chromatography Tandem Mass Spectrometry ◽  
Limit Of Quantitation ◽  
Liquid Chromatography Tandem Mass

ABSTRACT A fast and easy-to-use liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination and quantification of a novel antifungal drug, olorofim (F901318), a member of the novel class of orotomides, in human plasma and serum was developed and validated. Sample preparation was based on protein precipitation with acetonitrile and subsequent centrifugation. An isotope-labeled analogue of F901318 was employed as an internal standard. Chromatographic separation was achieved using a 50-mm by 2.1-mm, 1.9-μm, polar Hypersil Gold C18 column and isocratic mobile phase consisting of 0.1% formic acid–acetonitrile (60%-40%, vol/vol) at a flow rate of 330 μl/min. The analyte was detected using a triple-stage quadrupole mass spectrometer operated in selected reaction monitoring (SRM) mode with positive heated electrospray ionization (HESI+) within a single runtime of 2.00 min. The present LC-MS/MS method was validated according to the international guidelines of the International Conference on Harmonisation (ICH) and the U.S. Food and Drug Administration (FDA). Linearity of F901318 concentration ranges was verified by the Mandel test. The calibration curve was tested linear across the range and fitted using least-squares regression with a weighting factor of the reciprocal concentration. The limit of detection was 0.0011 mg/liter, and the lower limit of quantitation was 0.0033 mg/liter. Intraday and interday precisions ranged from 1.17% to 3.23% for F901318, and intraday and interday accuracies (percent bias) ranged from 0.75% to 5.01%. In conclusion, a method was established for the rapid quantitation of F901318 concentrations in serum and plasma samples in patient trials, and it optimizes therapeutic drug monitoring in applying an easy-to-use single method.

scholarly journals Development and Validation of an LC-MS/MS Based Method for the Determination of Deoxynivalenol and Its Modified Forms in Maize

Toxins ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 600
Author(s):  
Iris Fiby ◽  
Marta Magdalena Sopel ◽  
Herbert Michlmayr ◽  
Gerhard Adam ◽  
Franz Berthiller
Keyword(s):  
Matrix Effects ◽  
Internal Standard ◽  
Reversed Phase ◽  
Selected Reaction Monitoring ◽  
Stable Isotope Dilution ◽  
Liquid Chromatography Tandem Mass ◽  
Cereal Samples ◽  
Negative Electrospray Ionization ◽  
Development And Validation ◽  
Modified Forms

The Fusarium mycotoxin deoxynivalenol (DON) is a common contaminant of cereals and is often co-occurring with its modified forms DON-3-glucoside (D3G), 3-acetyl-DON (3ADON) or 15-acetyl-DON (15ADON). A stable-isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) based method for their determination in cereals was developed and validated for maize. Therefore, 13C-labelled D3G was enzymatically produced using 13C-DON and [13C6Glc]-sucrose and used as an internal standard (IS) for D3G, while uniformly 13C labelled IS was used for the other mycotoxins. Baseline separation was achieved for the critical peak pair DON/D3G, while 3ADON/15ADON could not be fully baseline separated after testing various reversed phase, fluorinated phase and chiral LC columns. After grinding, weighing and extracting the cereal samples, the raw extract was centrifuged and a mixture of the four 13C-labelled ISs was added directly in a microinsert vial. The subsequent analytical run took 7 min, followed by negative electrospray ionization and selected reaction monitoring on a triple quadrupole MS. Maize was used as a complex cereal model matrix for validation. The use of the IS corrected the occurring matrix effects efficiently from 76 to 98% for D3G, from 86 to 103% for DON, from 68 to 100% for 15ADON and from 63 to 96% for 3ADON.

scholarly journals Simultaneous LC-MS/MS Determination of Sacubitril, Valsartan and LBQ657 in Human Plasma and Its Application to Clinical Study

2021 ◽  
Author(s):  
Yufeng Ni ◽  
Yujia Zhang ◽  
Chong Zou ◽  
Li Ding
Keyword(s):  
Human Plasma ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Ionization Source ◽  
Internal Standards ◽  
Accuracy And Precision ◽  
Liquid Chromatography Tandem Mass ◽  
Multiple Reaction Monitoring Mode ◽  
Positive Ion

A rapid and reproducible liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated to simultaneously determine sacubitril, valsartan and a metabolite of sacubitril (LBQ657) in human plasma using sacubitril-d4 and valsartan-d3 as the internal standards. Following protein precipitation, the analytes were operated on an Ultimate® XB-C18 column (2.1 × 50 mm, 3.5 μm, Welch) with a gradient elution with acetonitrile, and 5 mM ammonium acetate and 0.1% formic acid in water as the mobile phase. The detection was performed on a Triple Quad™ 4000 mass spectrometer coupled with an electrospray ionization source (ESI) under positive-ion multiple reaction monitoring mode. The linearities are 2.00-4000, 5.00-10000 and 5.00-10000 ng mL-1 for sacubitril, valsartan and LBQ657, respectively. The accuracy and precision of intra- and inter-day, dilution accuracy, recovery and stability of the method were all within the acceptable limits and no matrix effect or carryover was observed. The suitability of the method was successfully demonstrated in terms of the quantification of sacubitril, valsartan and LBQ657 in plasma samples collected from healthy Chinese volunteers in a clinical trial.

scholarly journals Liquid Chromatography/Tandem Mass Spectrometry for the Simultaneous Determination of Alverine and its Metabolite, Monohydroxy Alverine, in Human Plasma: Application to a Pharmacokinetic Study

2011 ◽  
Vol 8 (1) ◽  
pp. 201-211 ◽  
Author(s):  
Rahul C. Gavhane ◽  
Ketan K. Nerurkar ◽  
Ashok M. Kalamkar ◽  
Mitesh R. Patil ◽  
Satish G. Pingale ◽  
...  
Keyword(s):  
Human Plasma ◽  
Pharmacokinetic Study ◽  
Solid Phase ◽  
Internal Standard ◽  
Selected Reaction Monitoring ◽  
Limit Of Quantification ◽  
Liquid Chromatography Tandem Mass ◽  
Assay Precision ◽  
Male Subjects

A rapid and sensitive LC-MS-MS method for the determination of alverine (ALV) and its major metabolite, monohydroxy alverine (MHA), in human plasma using imipramine as an internal standard was developed and validated. The analytes were extracted from 0.5 mL aliquots of human plasma by solid phase extraction, using oasis cartridge. Chromatographic separation was carried on Thermo Gold C18 column (50 × 4.6 mm, 5 μ) at 30 °C, with isocratic mobile phase, a flow rate of 0.4 mL/min and a total run time of 3.5 min. Detection and quantification were performed using a mass spectrometer in the selected reaction-monitoring mode with positive electrospray ionization atm/z282.3 → 91.11 for alverine,m/z298.3 → 106.9 for mono-hydroxy-alverine, andm/z281.0 → 86.0 for internal standard (IS) respectively. This assay was linear over a concentration range of 0.060-10 ng/mL with a lower limit of quantification of 0.060 ng/mL for both alverine and monohydroxy alverine. The coefficient of variation for the assay precision were <9.18% and <8.44%, the accuracy were >104.66% and >100.38% for alverine and monohydroxy alverine respectively. This method was successfully applied to a pharmacokinetic study after oral administration of alverine citrate 60 mg capsule in healthy male subjects.

Determination of cortisol in hair using liquid chromatography-tandem mass spectrometry: a short review

Bioanalysis ◽  
2021 ◽  
Author(s):  
Daniella Rheingantz Decker Soares ◽  
Marina Venzon Antunes ◽  
Rafael Linden
Keyword(s):  
Mass Spectrometry ◽  
Short Review ◽  
Reversed Phase ◽  
Negative Ion ◽  
Stress Evaluation ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Negative Ion Mode ◽  
Analytical Approaches

Cortisol is considered a particularly relevant biomarker in the context of stress evaluation. This study aims to review of the available literature on the determination of cortisol in hair using LC-MS/MS. Currently, there is no standardized procedure for the measurement of cortisol concentrations in hair, and different sample preparation, chromatographic separation and mass spectrometric detection conditions were described. Simple methanolic extraction, reversed-phase separation and MRM detection in negative ion mode are the most common employed analytical approaches. Reported assays presented acceptable sensitivity for clinical purposes. The increasing use of mass spectrometry in clinical laboratories may contribute to the establishment of LC-MS/MS as the method of choice for the determination of cortisol concentrations in hair.

scholarly journals Platelet-Activating Factor Quantification Using Reversed Phase Liquid Chromatography and Selected Reaction Monitoring in Negative Ion Mode

Lipids ◽  
2016 ◽  
Vol 51 (12) ◽  
pp. 1421-1425 ◽  
Author(s):  
Daniel P. Pike ◽  
Celine L. Hartman ◽  
Gregory J. Weissler ◽  
Elisa N. D. Palladino ◽  
Carolyn J. Albert ◽  
...  
Keyword(s):  
Liquid Chromatography ◽  
Platelet Activating Factor ◽  
Reversed Phase ◽  
Negative Ion ◽  
Selected Reaction Monitoring ◽  
Reaction Monitoring ◽  
Reversed Phase Liquid Chromatography ◽  
Phase Liquid ◽  
Negative Ion Mode

scholarly journals Variation in the Relative Isomer Abundance of Synthetic and Biologically Derived Phosphatidylethanols and Its Consequences for Reliable Quantification

2020 ◽  
Author(s):  
Marc Luginbühl ◽  
Reuben S E Young ◽  
Frederike Stoeth ◽  
Wolfgang Weinmann ◽  
Stephen J Blanksby ◽  
...  
Keyword(s):  
Reference Materials ◽  
Neutral Loss ◽  
Acyl Chain ◽  
Reversed Phase ◽  
Fatty Acyl ◽  
Negative Ion ◽  
Selected Reaction Monitoring ◽  
Fatty Acyl Chain ◽  
Blood Samples ◽  
Product Ions

Abstract Phosphatidylethanol (PEth) in human blood samples is a marker for alcohol usage. Typically, PEth is detected by reversed-phase liquid chromatography coupled with negative ion tandem mass spectrometry, investigating the fatty acyl anions released from the precursor ion upon collision-induced dissociation (CID). It has been established that in other classes of asymmetric glycerophospholipids, the unimolecular fragmentation upon CID is biased depending on the relative position (known as sn-position) of each fatty acyl chain on the glycerol backbone. As such, the use of product ions in selected-reaction-monitoring (SRM) transitions could be prone to variability if more than one regioisomer is present in either the reference materials or the sample. Here, we have investigated the regioisomeric purity of three reference materials supplied by different vendors, labeled as PEth 16:0/18:1. Using CID coupled with ozone-induced dissociation, the regioisomeric purity (% 16:0 at sn-1) was determined to be 76, 80 and 99%. The parallel investigation of the negative ion CID mass spectra of standards revealed differences in product ion ratios for both fatty acyl chain product ions and ketene neutral loss product ions. Furthermore, investigation of the product ion abundances in CID spectra of PEth within authentic blood samples appears to indicate a limited natural variation in isomer populations between samples, with the cannonical, PEth 16:0/18:1 (16:0 at sn-1) predominant in all cases. Different reference material isomer distributions led to variation in fully automated quantification of PEth in 56 authentic dried blood spot (DBS) samples when a single quantifier ion was used. Our results suggest caution in ensuring that the regioisomeric compositions of reference materials are well-matched with those of the authentic blood samples.

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