Development and Application of Immunoaffinity Column Purification and Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectrometry for Determination of Domoic Acid in Shellfish

Domoic acid (DA) is a neurotoxin associated with amnesic shellfish poisoning (ASP). Though LC coupled to tandem mass spectrometry (LC-MS/MS) has become the preferred method for DA determination, traditional sample pretreatment is still labor-intensive. In this study, a simple, efficient and selective method for LC-MS/MS analysis of DA in shellfish was established by optimizing clean-up procedures on a self-assembly immunoaffinity column (IAC). Shellfish was extracted with 75% methanol twice and diluted with phosphate buffered saline (PBS, 1:2). The mixture was purified on IAC as follows: preconditioned with PBS, loaded with sample, washed by 50% MeOH, and eluted with MeOH containing 2% ammonium hydroxide. Concentrated analyte was monitored by multiple reaction monitoring (MRM) using electrospray (ESI) positive ion mode throughout the LC gradient elution. Based on the post-extraction addition method, matrix effects for various shellfish matrices were found to be less than 8%. The developed method was fully validated by choosing mussel as the representative matrix. The method had a limit of detection (LOD) of 0.02 µg·g−1, showed excellent linear correlation in the range of 0.05–40 µg·g−1, and obtained ideal recoveries (91–94%), intra-day RSDs (6–8%) and inter-day RSDs (3–6%). The method was successfully applied to DA determination in 59 shellfish samples, with a detection rate of 10% and contaminated content of 0.1–14.9 µg·g−1.

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METHOD DEVELOPMENT AND VALIDATION OF LERCANIDIPINE IN HUMAN PLASMA BY LIQUID CHROMATOGRAPHY TANDEM-MASS SPECTROMETRY

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018v10i4.26544 ◽

2018 ◽

Vol 10 (4) ◽

pp. 87

Author(s):

Yahdiana Harahap ◽

Norma Andriyani ◽

Harmita .

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Method Development ◽

Matrix Effects ◽

Multiple Reaction Monitoring ◽

Tandem Mass ◽

Mass Detection ◽

Column Temperature ◽

Z Value

Objective: To obtain an optimum and validated method for analyzing lercanidipine in plasma using Ultra Performance Liquid Chromatography of Tandem Mass Spectrometry (UPLC-MS/MS).Methods: The separation was carried out using 1.7μm (2.1 x 100 mm) Waters AcquityTM UPLC C18 column, a mobile phase of the 0.1% formic acid-methanol mixture (20:80 v/v) with isocratic elution, 30 °C column temperature, 0.2 ml/min flow rate and amlodipine as an internal standard. Mass detection was performed with a positive XBL TQD type Electrospray Ionization (ESI) in Multiple Reaction Monitoring modes. Lercanidipine was detected at m/z value of 612.11>280.27 and amlodipine was detected at m/z value 409.1>238.15. The optimum sample preparation method was a liquid-liquid extraction using 5 ml of n-hexane-ethyl acetate (50:50 v/v), vortex mixed for 3 min, centrifuged at 4000 rpm for 20 min, evaporated with nitrogen at 50 °C for 30 min, and the residue was reconstituted with 100 μl of mobile phase.Results: The method was linear in the range of 0.025-10 ng/ml with r ≥ 0.9986. Accuracy and precision within-run and between-run met the requirements with %diff and %CV, not exceeding ± 15% and not more than ± 20% for Lower Limit of Quantification (LLOQ) concentration.Conclusion: It was concluded that the developed method met the requirements of selectivity, carry over, stability, the integrity of dilution, and matrix effects under the Guideline on Bioanalytical Method Validation by the European Medicines Agency in 2011.

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Simultaneous Quantitation of Seven Phenethylamine-Type Drugs in Forensic Blood and Urine Samples by UHPLC–MS-MS

Journal of Analytical Toxicology ◽

10.1093/jat/bkab014 ◽

2021 ◽

Author(s):

Chu-An Yang ◽

Hsiu-Chuan Liu ◽

Ray H Liu ◽

Dong-Liang Lin ◽

Shu-Pao Wu

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Limit Of Detection ◽

Multiple Reaction Monitoring ◽

Analytical Data ◽

Tandem Mass ◽

Limit Of Quantitation ◽

Routine Identification ◽

Urine Specimens

Abstract Abuse of new psychoactive substances (NPS) has become a health and social issue of global concern. p-Methoxyamphetamine (PMA)/p-methoxymethamphetamine (PMMA) with fluoro- or chloro-derivatives of amphetamine and methamphetamine were among the most common drugs found in specimens from fatal cases in Taiwan during the January 2011 to December 2018 period. A liquid–liquid extraction sample preparation protocol with highly sensitive ultra-high performance liquid chromatography–tandem mass spectrometry approach was developed for the simultaneous analysis of seven phenethylamine-type drugs—PMA, PMMA, p-methoxyethylamphetamine, 4-fluoroamphetamine (4-FA), 4-fluoromethamphetamine (4-FMA), 4-chloroamphetamine (4-CA) and 4-chloromethamphetamine (4-CMA)—in postmortem blood and urine specimens. Separation by liquid chromatography was performed by Agilent Zorbax SB-Aq column. Tandem mass spectrometry was operated in Agilent Jet Stream Technology electrospray ionization in positive-ion multiple reaction monitoring mode. An analytical methodology was evaluated using drug-free blood and urine after fortification with 100–2,000 ng/mL of the seven target analytes. Average extraction recoveries were >80%; slightly higher ion suppression was observed for PMA and 4-CA; intra-/inter-day precision (% coefficient of variation) and accuracy were in the ranges of 0.52–12.3% and 85–110%, respectively. Limit of detection and lower limit of quantitation for these seven analytes were both in the 0.5–5 ng/mL range. Interference and carryover were not significant. This relatively simple methodology was found effective and reliable for routine identification and quantitation of these seven analytes in postmortem and antemortem blood and urine specimens received in 2018. Analytical data obtained from these actual cases indicated the following: (i) compared to findings reported during the 2007–2011 period, the use of substituted phenethylamine-type drugs decreased in 2018; (ii) ketamine and 7-aminonimetazepam (the main metabolite of nimetazepam) were the most common co-ingested substances in specimens containing PMA/PMMA, 4-FA/4-FMA, or 4-CA/4-CMA; and (iii) in drug fatalities, the concentration of PMA was significantly higher than the concentration of PMMA in both urine and blood, while the reverse was true in urine specimens from antemortem cases.

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Application of a Reliable LC-MS/MS Method for Determination of Rizatriptan in Healthy Subject Samples: Demonstration of Assay Reproducibility by Incurred Sample Reanalysis

ISRN Chromatography ◽

10.5402/2012/761679 ◽

2012 ◽

Vol 2012 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Dinesh S. Patel ◽

Naveen Sharma ◽

Mukesh C. Patel ◽

Bhavin N. Patel ◽

Pranav S. Shrivastav ◽

...

Keyword(s):

Mass Spectrometry ◽

Quality Control ◽

Tandem Mass Spectrometry ◽

Human Plasma ◽

Dynamic Range ◽

Limit Of Detection ◽

Multiple Reaction Monitoring ◽

Tandem Mass ◽

Limit Of Quantitation

A reliable, rapid, and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay has been proposed for the determination of rizatriptan in human plasma using sumatriptan as internal standard (IS). The analyte and IS were extracted from 300 μL human plasma via liquid-liquid extraction and the chromatography was achieved on Hypurity C18 (50 mm × 4.6 mm, 5 μm) column under isocratic conditions. Detection of rizatriptan and IS was done by tandem mass spectrometry, operating in positive ionization and multiple-reaction monitoring mode. The limit of detection and lower limit of quantitation of the method were 0.04 and 0.20 ng/mL, respectively, with a linear dynamic range of 0.20–60.0 ng/mL. The intrabatch and interbatch precision (% CV) was ≤8.4% while the mean extraction recovery was >78% across quality control levels. Bench top stability, freeze and thaw stability, processed sample stability, and long-term stability in plasma were evaluated at two quality control levels. It was successfully applied to a bioequivalence study of 10 mg rizatriptan orally disintegrating tablet formulation in 40 and 32 healthy Indian male subjects under fasting and fed conditions, respectively. The reproducibility in the measurement of study data was demonstrated by reanalysis of 254 incurred samples.

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Amnesic Shellfish Poisoning Toxins in Shellfish: Estimation of Uncertainty of Measurement for a Liquid Chromatography/Tandem Mass Spectrometry Method

Journal of AOAC International ◽

10.1093/jaoac/86.5.1095 ◽

2003 ◽

Vol 86 (5) ◽

pp. 1095-1100 ◽

Cited By ~ 16

Author(s):

Patrick T Holland ◽

Paul McNabb ◽

Andrew I Selwood ◽

Tracey Neil

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Domoic Acid ◽

Matrix Effects ◽

Multiple Reaction Monitoring ◽

Tissue Homogenate ◽

Uncertainty Of Measurement ◽

Shellfish Poisoning ◽

Total Uncertainty ◽

Amnesic Shellfish Poisoning

Abstract A liquid chromatography/mass spectrometry (LC/MS) method for amnesic shellfish poisoning toxins in shellfish was developed and validated. Tissue homogenate (4 g) was extracted with 16 mL methanol–water (1 + 1, v/v). Dilution into acetonitrile–water (1 + 9, v/v) was followed by C18 solid-phase extraction cleanup. Domoic acid (DA) and epi-domoic acid were determined by LC/MS/MS with electrospray ionization and multiple reaction monitoring. External calibration was performed with dilutions of a certified reference standard. Advantages of this method include speed, lower detection limits, and a very high degree of specificity. The LC/MS response was highly linear, and there were no significant interferences to the determination of DA. Formal method validation was performed on 4 shellfish species. Fortification studies gave recoveries (mean ± SD; n = 24) of 93 ± 14% at 1 mg/kg, and 93.3 ± 7.6% at 20 mg/kg over all the species. Analysis of a mussel certified reference material showed the bias as <5%. The limits of detection and quantitation were 0.15 and 0.5 mg/kg, respectively. Routine application of the method over 4 months gave a recovery for the QC sample (1 mg/kg fortified blank mussel homogenate) run with each batch of 88.9 ± 5.5% (mean ± SD; n = 37). The total uncertainty of measurement results were estimated as 0.12 (12%) at 0.25–5 mg/kg and 0.079 (7.9%) at 5–50 mg/kg. The major contribution to the uncertainty was the repeatability of the LC/MS determination, probably arising from subtle matrix effects.

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Use of Deuterated Internal Standards for Quantitation of T-2 and HT-2 Toxins in Human Blood by Tandem Mass Spectrometry

Journal of AOAC INTERNATIONAL ◽

10.1093/jaoac/72.5.807 ◽

1989 ◽

Vol 72 (5) ◽

pp. 807-812 ◽

Cited By ~ 1

Author(s):

Robert J Pawlosky ◽

Chester J Mirocha ◽

Y Wen ◽

Hamed K Abbas

Keyword(s):

Mass Spectrometry ◽

Detection Limit ◽

Tandem Mass Spectrometry ◽

Human Blood ◽

Limit Of Detection ◽

Multiple Reaction Monitoring ◽

Tandem Mass ◽

Reaction Monitoring ◽

Internal Standards ◽

Selection Of

Abstract Deuterated acetyl derivatives (3-trideutero-acetyl-T-2 and 15-trideutero- HT-2) were prepared for use as internal standards for the quantitation of T-2 and HT-2 in blood by tandem mass spectrometry. The method used was multiple reaction monitoring (MRM), which essentially involves the selection of a parent ion for analysis followed by monitoring of the daughter ions generated by collision activated decomposition. The parent ions chosen for the trifluoroacetate derivative of T-2 and HT-2 were m/z+ 478 and 532, respectively. Both parents yield the same daughter ions, i.e., 180, 138, and 121. HT-2 and T-2 were added to blood extracts in amounts ranging from 1 to 20 ppb. The limit of detection is about 0.5 ppb with an effective detection limit of 1.0 ppb in a range of 1-20 ppb. The recovery is about 90%. This method can be used by veterinarians for purposes of diagnostics. It can be used for urine as well as blood.

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Simultaneous determination of multi – component mycotoxin in feeds by liquid chromatography – tandem mass spectrometry

Bulletin of the Veterinary Institute in Pulawy ◽

10.2478/bvip-2013-0097 ◽

2013 ◽

Vol 57 (4) ◽

pp. 567-572 ◽

Cited By ~ 4

Author(s):

Katarzyna Pietruszka ◽

Bartosz Sell ◽

Olga Burek ◽

Henryka Wiśniewska-Dmytrow

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Ion Trap ◽

Limit Of Detection ◽

Multiple Reaction Monitoring ◽

Negative Ion ◽

Tandem Mass ◽

Penicillium Species ◽

Liquid Chromatography Tandem Mass

Abstract A multiresidue method for determination and quantification of Fusarium mycotoxins: deoxynivalenol, zearalenone, T-2 toxin, HT-2 toxin, and metabolite of Aspergillus and Penicillium species - ochratoxin A in feeds was described. The method was based on the simultaneous extraction of selected mycotoxins from matrix, followed by liquid chromatography coupled with tandem mass spectrometry using a hybrid triple quadrupole - linear ion trap mass spectrometer with the multiple reaction monitoring in both positive- and negative-ion modes. The method was validated in accordance with the Commision Decision 2002/657/EC requirements. The mean recoveries of mycotoxins from spiked feed samples ranged from 74.6% to 113.9%, whereas limit of detection and quantification ranged from 0.72 to 12.4 μg/kg and 1.86 to 31.7 μg/kg, respectively.

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Pharmacokinetics and Bioavailability Study of Tubeimoside I in ICR Mice by UPLC-MS/MS

Journal of Analytical Methods in Chemistry ◽

10.1155/2018/9074893 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Lianguo Chen ◽

Qinghua Weng ◽

Feifei Li ◽

Jinlai Liu ◽

Xueliang Zhang ◽

...

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Oral Absorption ◽

Matrix Effects ◽

Multiple Reaction Monitoring ◽

Internal Standard ◽

Tandem Mass ◽

Relative Standard ◽

Bioavailability Study ◽

Tubeimoside I

The aim of this study is to establish and validate a rapid, selective, and sensitive ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to determine tubeimoside I (TBMS-I) in ICR (Institute of Cancer Research) mouse whole blood and its application in the pharmacokinetics and bioavailability study. The blood samples were precipitated by acetonitrile to extract the analytes. Chromatographic separation was performed on a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm). The mobile phase consisted of water with 0.1% formic acid and methanol (1 : 1, v/v) at a flow rate of 0.4 mL/min. The total eluting time was 4 min. The TBMS-I and ardisiacrispin A (internal standard (IS)) were quantitatively detected by a tandem mass spectrometry equipped with an electrospray ionization (ESI) in a positive mode by multiple reaction monitoring (MRM). A validation of this method was in accordance with the US Food and Drug Administration (FDA) guidelines. The lower limit of quantification (LLOQ) of TBMS-I was 2 ng/mL, and the calibration curve was linearly ranged from 2 to 2000 ng/mL (r2 ≥ 0.995). The relative standard deviation (RSD) of interday precision and intraday precision was both lower than 15%, and the accuracy was between 91.7% and 108.0%. The average recovery was >66.9%, and the matrix effects were from 104.8% to 111.0%. In this assay, a fast, highly sensitive, and reproducible quantitative method was developed and validated in mouse blood for the first time. The absolute availability of TBMS-I in the mouse was only 1%, exhibiting a poor oral absorption.

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A novel MS3 experiment for quantifying ions with a linear ion trap

Canadian Journal of Chemistry ◽

10.1139/cjc-2017-0734 ◽

2018 ◽

Vol 96 (7) ◽

pp. 653-663 ◽

Cited By ~ 1

Author(s):

J. Larry Campbell ◽

Bruce A. Collings ◽

J.C. Yves Le Blanc ◽

James W. Hager

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Ion Trap ◽

Matrix Effects ◽

Multiple Reaction Monitoring ◽

Analytical Signal ◽

Linear Ion Trap ◽

Tandem Mass ◽

High Background ◽

Cycle Times

Liquid chromatography coupled with tandem mass spectrometry has long been employed for the quantitation of molecules. With judicious selection of precursor and fragment ions, multiple-reaction monitoring assays can be developed rapidly for these experiments. However, there are cases where analyses struggle due to high background signals caused by matrix effects that interfere with the analytical signal. An alternative to MRMs involves using two stages of tandem mass spectrometry — an MS3 experiment. Although this technique can provide greater selectivity than MS/MS experiments, cycle times for MS3 experiments are typically longer than MRM-type experiments. Here, we present a quantitation technique employing an MS3 method with shorter cycle times than traditional linear ion trap MS3 scans. Termed “scan-free” MS3, this technique performs “mass analysis” by isolating the ions of interest in the linear ion trap and then emptying the trap of these ions. The signal will be due only to those preselected ions, resulting in an MS3 experiment with up to a ∼35% reduction in cycle times relative to standard MS3 experiments without loss of sensitivity. We compare the analytical performance of this method with MRMs, as well as standard MS3 experiments, finding equivalent or better performance from the scan-free MS3 method.

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Determination of Pesticides in Soy-Based Infant Formula Using Liquid Chromatography with Electrospray Ionization Tandem Mass Spectrometry

Journal of AOAC International ◽

10.1093/jaoac/89.1.214 ◽

2006 ◽

Vol 89 (1) ◽

pp. 214-224 ◽

Cited By ~ 11

Author(s):

Jian Wang ◽

Wendy Cheung

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Electrospray Ionization ◽

Infant Formula ◽

Matrix Effects ◽

Multiple Reaction Monitoring ◽

Tandem Mass ◽

Calibration Curves ◽

Ionization Tandem Mass Spectrometry

Abstract A sensitive method using liquid chromatography with electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) was developed and validated to quantify and confirm 13 pesticides, including aldicarb sulfoxide, aldicarb sulfone, oxamyl, methomyl, formetanate, 3-hydroxycarbofuran, carbendazim, thiabendazole, aldicarb, propoxur, carbofuran, carbaryl, and methiocarb, in soy-based infant formula. Data acquisition under MS/MS was achieved by applying multiple reaction monitoring of 2 fragment ion transitions to provide a high degree of sensitivity and selectivity for both quantitation and confirmation. Different approaches to constructing calibration curves were compared and discussed to address issues of the extraction efficiency or recovery, and matrix effects. Matrix-matched standard calibration curves with the use of isoprocarb as an internal standard were finally used to achieve the best accuracy of the method. Under most circumstances, recoveries of 13 pesticides, spiked at 5.0, 25.0, and 45.0 g/kg, were close to 100%. The method detection limits (signal-to-noise ratio 3:1; g/kg) of 13 pesticides were 0.2 for thiabendazole and methiocarb, 0.6 for aldicarb, and 0.1 for the others.

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Analysis of Polycyclic Aromatic Hydrocarbon in Airborne Particulate Matter Samples by Gas Chromatography in Combination with Tandem Mass Spectrometry (GC-MS/MS)

Journal of Analytical Methods in Chemistry ◽

10.1155/2021/6641326 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Nam Vu-Duc ◽

Lan Anh Phung Thi ◽

Thuy Le-Minh ◽

Lan-Anh Nguyen ◽

Huong Nguyen-Thi ◽

...

Keyword(s):

Mass Spectrometry ◽

Gas Chromatography ◽

Particulate Matter ◽

Tandem Mass Spectrometry ◽

Proficiency Testing ◽

Limit Of Detection ◽

Solid Phase ◽

Multiple Reaction Monitoring ◽

Tandem Mass ◽

Polycyclic Aromatic

Polycyclic aromatic hydrocarbons (PAHs), the family of organic contaminations, have been shown to have negative effects on human health. However, until now, the comprehension on occurrence, distribution, and risk assessment of human exposure to PAHs has been limited in Vietnam. In this work, a capillary gas chromatography coupled with electron impact ionization tandem mass spectrometry (GC-EI-MS/MS) has been introduced for analysis of 16 PAHs in some particulate matter samples. PAHs have been separated on the TG 5 ms capillary gas chromatographic column and detected by tandem mass spectrometry in multiple reaction monitoring mode. The PAHs in the particulate matter (PM 2.5 and PM 10) samples were extracted by ultrasonic-assisted liquid extraction and cleaned up by an acidic silica gel solid phase extraction. The linearity range of all analyzed PAHs was from 5 to 2000 ng mL−1 with R2 ≥0.9990. Limit of detection (LOD) of PAHs in particulate matter sample was from 0.001 ng m−3 (Br-Naph) to 0.276 ng m−3 (Fln). The recovery of PAHs was investigated by international proficiency testing samples. The recoveries of PAHs in proficiency testing sample ranged from 79.3% (Chr) to 109.8% (IcdP). The in-house validated GC-EI-MS/MS method was then applied to analysis of some particulate matter samples that were collected in the Hanoi areas. The total concentrations of PAHs in several brands of samples collected from Hanoi were found in the range of 226.3 ng m−3–706.43 ng m−3. Among the studied compounds, naphthalene was found at high frequency and ranged from 106.5 ng m−3 to 631.1 ng m−3. The main distribution of the PAHs in particulate matter samples was two-ring and three-ring compounds.

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