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

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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Determination of Cyclamate in Foods by Ultraperformance Liquid Chromatography/Tandem Mass Spectrometry

Journal of AOAC International ◽

10.1093/jaoac/91.5.1095 ◽

2008 ◽

Vol 91 (5) ◽

pp. 1095-1102 ◽

Cited By ~ 7

Author(s):

Robert Sheridan ◽

Thomas King

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Sample Preparation ◽

Tandem Mass Spectrometry ◽

Limit Of Detection ◽

Tandem Mass ◽

Chromatography Tandem Mass Spectrometry ◽

Limit Of Quantitation ◽

Liquid Chromatography Tandem Mass

Abstract A highly sensitive and selective method that requires minimal sample preparation was developed for the confirmation and quantitation of cyclamate in a variety of foods by high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). Sample preparation consisted of homogenization followed by extraction and dilution of cyclamate with water. HPLC separation was achieved using a bridged ethyl hybrid C18 high-pressure column with a mobile phase consisting of 0.15 acetic acid and methanol. Under electrospray ionization negative conditions, quantitation was achieved by monitoring the fragment m/z 79.7 while also collecting parent ion m/z 177.9. Two food matrixes, diet soda and jelly, were subjected to a validation procedure in order to evaluate the applicability of the method. The cyclamate limit of detection for both matrixes was determined to be 0.050 g/g with a limit of quantitation of 0.150 g/g. The correlation coefficient of the calibration curves was >0.9998 from 0.0005 to 0.100 g/mL. The method has been used for the determination of cyclamate in several foods and the results are presented.

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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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Quantification of Cefepime, Meropenem, Piperacillin, and Tazobactam in Human Plasma Using a Sensitive and Robust Liquid Chromatography-Tandem Mass Spectrometry Method, Part 1: Assay Development and Validation

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00859-18 ◽

2018 ◽

Vol 62 (9) ◽

Cited By ~ 2

Author(s):

Ronilda D'Cunha ◽

Thanh Bach ◽

Beth Ann Young ◽

Peizhi Li ◽

Demet Nalbant ◽

...

Keyword(s):

Mass Spectrometry ◽

Tandem Mass Spectrometry ◽

Human Plasma ◽

Dynamic Range ◽

Multiple Reaction Monitoring ◽

Plasma Concentrations ◽

Extraction Procedure ◽

Gradient Elution ◽

Tandem Mass ◽

Sample Extraction

ABSTRACTThe highly variable pharmacokinetics of β-lactam antibiotics and β-lactamase inhibitors poses a significant challenge to clinicians in ensuring appropriate antibiotic doses in critically ill patients. Therefore, routine monitoring of plasma concentrations is important for individualization of antimicrobial therapy. Accordingly, a simple and robust analytical method for the simultaneous measurement of multiple β-lactam antibiotics and β-lactamase inhibitors is highly desirable to ensure quick decisions on dose adjustments. In this study, a sensitive, simple, and robust method for the simultaneous quantification of cefepime, meropenem, piperacillin, and tazobactam in human plasma was developed and rigorously validated according to FDA guidance. Sample extraction was accomplished by simple protein precipitation. Chromatographic separation of analytes was achieved using stepwise gradient elution. Analytes were monitored using tandem mass spectrometry (MS/MS) with a turbo ion spray source in positive multiple-reaction-monitoring mode. The calibration curve ranged from 0.5 to 150 μg/ml for cefepime, 0.1 to 150 μg/ml for meropenem and piperacillin, and 0.25 to 150 μg/ml for tazobactam. Inter- and intraday precision and accuracy, sensitivity, selectivity, dilution integrity, matrix effect, extraction recovery, and hemolysis effect were investigated for all four analytes, and the results met the acceptance criteria. Compared to other reported methods, our method is more robust because of the combination of the following features: (i) a simple sample extraction procedure, (ii) a short sample run time, (iii) a wide dynamic range, and (iv) the small plasma sample volume needed. Since our method already covers β-lactams and a β-lactamase inhibitor with highly heterogeneous physicochemical properties, further antibiotic candidates may easily be incorporated into this multianalyte method.

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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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Rapid Determination of Fosetyl-Aluminum Residues in Lettuce by Liquid Chromatography/Electrospray Tandem Mass Spectrometry

Journal of AOAC International ◽

10.1093/jaoac/86.4.832 ◽

2003 ◽

Vol 86 (4) ◽

pp. 832-838 ◽

Cited By ~ 27

Author(s):

Félix Hernández ◽

Juan V Sancho ◽

Óscar J Pozo ◽

Carme Villaplana ◽

María Ibáñez ◽

...

Keyword(s):

Mass Spectrometry ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Limit Of Detection ◽

Rapid Determination ◽

Tandem Mass ◽

Electrospray Tandem Mass Spectrometry ◽

Relative Standard ◽

Limit Of Quantitation

Abstract This paper describes a new method for the sensitive and selective determination of fosetyl-aluminum (Al) residues in vegetable samples. The method involves extraction with water by using a high-speed blender and subsequent injection of the 5-fold diluted extract into the liquid chromatograph. Fosetyl-Al is determined by liquid chromatography with electrospray tandem mass spectrometry after the addition of tetrabutylammonium acetate as the ion-pairing re-agent. The method has been used to assay lettuce samples spiked at 2 and 0.2 mg/kg. Recoveries were satisfactory, with mean values of 98 and 106%, respectively, and relative standard deviations were <10%. The limit of quantitation was 0.2 mg/kg, and the limit of detection was as low as 0.05 mg/kg. Matrix-matched calibration was used for quantitation, and the addition of an internal standard improved repeatability. The developed method allows the accurate and rapid determination of low levels of fosetyl-Al residues in lettuce with very little sample handling and good sensitivity; it was shown to be robust by the analysis of almost 100 samples.

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Quantitation of nitrofurantoin in human plasma by liquid chromatography tandem mass spectrometry

Acta Pharmaceutica ◽

10.2478/acph-2013-0012 ◽

2013 ◽

Vol 63 (2) ◽

pp. 141-158 ◽

Cited By ~ 6

Author(s):

Dinesh S. Patel ◽

Naveen Sharma ◽

Mukesh C. Patel ◽

Bhavin N. Patel ◽

Pranav S. Shrivastav ◽

...

Keyword(s):

Human Plasma ◽

Dynamic Range ◽

Limit Of Detection ◽

Multiple Reaction Monitoring ◽

Bioequivalence Study ◽

Capsule Formulation ◽

Limit Of Quantitation ◽

Liquid Chromatography Tandem Mass ◽

The Mean

A reliable, selective and sensitive LC-MS/MS assay has been proposed for the determination of nitrofurantoin in human plasma. The analyte and nitrofurazone were extracted from 100 μL of human plasma via SPE on Strata-X 33 μm extraction cartridges. Chromatography was done on a BDS Hypersil C18 (100 mm × 4.6 mm, 5 μm) column under isocratic conditions. Quantitation was done using the multiple reaction monitoring (MRM) mode for deprotonated precursor to product ion transitions of nitrofurantoin (m/z 237.0 → 151.8) and nitrofurazone (m/z 197.0 → 123.9). The limit of detection and the lowest limit of quantitation of the method were 0.25 ng mL-1 and 5.00 ng mL-1, respectively, with a linear dynamic range of 5.00-1500 ng mL-1 for nitrofurantoin. The intra- -batch and inter-batch precision (RSD, %) was ≤ 5.8 %, while the mean extraction recovery was > 92 %. The method was successfully applied to a bioequivalence study of a 100 mg nitrofurantoin capsule formulation in 36 healthy subjects.

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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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