scholarly journals Determination of Cyanide in Blood for Forensic Toxicology Purposes—A Novel Nci Gc-Ms/Ms Technique

Molecules ◽  
2021 ◽  
Vol 26 (18) ◽  
pp. 5638
Author(s):  
Marcin Osak ◽  
Grzegorz Buszewicz ◽  
Jacek Baj ◽  
Grzegorz Teresiński
Keyword(s):  
Phase Transfer ◽  
Multiple Reaction Monitoring ◽  
Forensic Toxicology ◽  
Optimal Parameters ◽  
Triple Quadrupole Mass Spectrometer ◽  
Matrix Interferences ◽  
Toxicological Studies ◽  
Validation Parameters ◽  
Pentafluorobenzyl Bromide

One of the recently evolving methods for cyanide determination in body fluids is GC-MS, following extractive alkylation with pentafluorobenzyl bromide or pentafluorobenzyl p-toluenesulfonate. The aim of this study was to improve previous GC methods by utilizing a triple quadrupole mass spectrometer, which could enhance selectivity and sensitivity allowing for the reliable confirmation of cyanide exposure in toxicological studies. Another purpose of this study was to facilitate a case investigation including a determination of cyanide in blood and to use the obtained data to confirm the ingestion of a substance, found together with a human corpse at the forensic scene. The blood samples were prepared following extractive alkylation with a phase transfer catalyst tetrabutylammonium sulfate and the PFB-Br derivatization agent. Optimal parameters for detection, including ionization type and multiple reaction monitoring (MRM) transitions had been investigated and then selected. The validation parameters for the above method were as follows—linear regression R2 = 0.9997 in the range of 0.1 µg/mL to 10 µg/mL; LOD = 24 ng/mL; LOQ = 80 ng/mL and an average recovery of extraction of 98%. Our study demonstrates the first attempt of cyanide determination in blood with gas chromatography-tandem mass spectrometry. The established method could be applied in forensic studies due to MS/MS confirmation of organic cyanide derivative and low matrix interferences owning to utilizing negative chemical ionization.

Simultaneous and Sensitive Determination of Amphetamine, Codeine and Morphine in Exhaled Breath Condensate, Using Capillary Electrophoresis Coupled with On-line and Off-line Enhancing Methods

2020 ◽  
Vol 16 (7) ◽  
pp. 872-879
Author(s):  
Samin Hamidi
Keyword(s):  
Drugs Of Abuse ◽  
Exhaled Breath Condensate ◽  
Direct Injection ◽  
Forensic Toxicology ◽  
Analytical Signal ◽  
Exhaled Breath ◽  
Concentration Method ◽  
Validation Parameters ◽  
Breath Condensate

Background: Abuse of drugs is associated with several medical, forensic, toxicology and social challenges. “Drugs of abuse” testing is therefore an important issue. Objective: We propose a simple CE-based method for the quantification of amphetamine, codeine and morphine after direct injection of Exhaled Breath Condensate (EBC) by the aid of simple stacking mode and an off-line pre-concentration method. Methods: Using graphene oxide adsorbents, amphetamine, codeine and morphine were extracted from EBC in order to eliminate the proteins and other interferences. In addition to off-line method, an online stacking mode was applied to improve the analytical signal obtained from the instrument. Results: The validation parameters were experimented on the developed method based on the FDA guideline over concentration ranges of 12.5-100, 30-500 and 10-1250 ng/mL associated with amphetamine, codeine and morphine, respectively. Small volumes (around 100 μL) of EBC were collected using a lab-made setup and successfully analyzed using the proposed method where precisions and accuracies (within day and between days) were in accordance with the guideline (recommended less than 15 % for biological samples). The recovery tests were used to evaluate the matrix effect and data (94 to 105 %) showed that the proposed method can be applied in different EBC matrix samplings of subjects. Conclusion: The proposed method is superior for simultaneous determination of amphetamine, codeine and morphine over chromatographic analyses because it is fast and consumes fewer chemicals, with no derivatization step.

scholarly journals UHPLC-QQQ-MS/MS assay for quantification of dianthrones as potential toxic markers of Polygonum multiflorum Thunb: Application to the standardization of TCMs with endogenous toxicity

2021 ◽  
Author(s):  
Jian-Bo Yang ◽  
Yun-Fei Song ◽  
Yue Liu ◽  
Hui-Yu Gao ◽  
Qi Wang ◽  
...  
Keyword(s):  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Triple Quadrupole ◽  
Quadrupole Mass ◽  
Polygonum Multiflorum ◽  
Triple Quadrupole Mass Spectrometer ◽  
Benefit Risk Assessment ◽  
Heparg Cells

Abstract Background: The raw and processed roots of Polygonum multiflorum Thunb (PM) are commonly used in clinical practice to treat diverse diseases; however, the reports of hepatotoxicity induced by Polygoni Multiflori Radix (PMR) and Polygoni Multiflori Radix Praeparata (PMRP) have emerged worldwide. Thus, it is necessary for researcher to explore the methods to improve its quality standards and further ensure its quality and treatment effect.Methods: In the present study, an ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-QQQ- MS/MS) method has been optimized and validated for the determination of dianthrones in PMR and PMRP, using bianthronyl as the internal standard. Chromatographic separation with a gradient mobile phase (A: acetonitrile and B: water containing 0.1% formic acid (v/v)) at a flow rate of 0.25 mL/min was achieved on a Waters Acquilty UPLC BEH b) C18 column (2.1 mm × 50 mm, 1.7 µm). A triple quadrupole mass spectrometer (TQMS) was operated in negative ionization mode with multiple reaction monitoring for the quantitative analysis of six dianthrones. Meanwhile, compounds 5 and 6 were further evaluated for cytotoxicity of HepaRG cells by CCK8 assay.Results: The UHPLC-QQQ-MS/MS method was first developed to simultaneous determination of six dianthrones in PMR and PMRP, namely polygonumnolides C1–C4 (1–4), trans-emodin dianthrones (5), and cis-emodin dianthrones (6). The contents of 1~6 in 90 batches of PMR were in the range of 0.027-19.04, 0.022-13.86, 0.073 -15.53, 0.034 -23.35, 0.38-83.67 and 0.29 -67.00 µg/g, respectively. The contents of 1~6 in 86 batches of commercial PMRP were in the range of 0.020-13.03, 0.051-8.94, 0.022-7.23, 0.030 -12.75, 0.098-28.54 and 0.14-27.79 µg/g, respectively. The six dianthrones were almost completely gone after reasonable processing for 24 h. Meanwhile, compounds 5 and 6 showed the inhibitory activity against HepaRG cells with the IC50 values of 10.98 and 15.45 μM, respectively. Furthermore, a systematic five-step strategy to realize the standardization of TCMs with endogenous toxicity is proposed for the first time, involving the establishment of determination methods, determination of the toxic markers, the standardization of processing method, the development of limit standards and benefit-risk assessment.Conclusion: The results of cytotoxicity evaluation of dianthrone indicated that trans-emodin dianthrones (5) and cis-emodin dianthrones (6) could be selected as the toxic markers of PMRP. Taking PMR and PMRP for example, we hope this study provided insight into the standardization and internationalization of endogenous toxic TCMs, with the main purpose of improving public health by scientifically using TCMs to treat diverse complex diseases in future.

High-throughput LC-MS/MS Method for Simultaneous Determination of Pantoprazole and Atorvastatin in Rat Plasma: Application to a Pharmacokinetic Interaction Study

2021 ◽  
Vol 22 ◽  
Author(s):  
Jian Le ◽  
Yuehua Liao ◽  
Shengni Li ◽  
Xiujuan Chen ◽  
Zhanying Hong
Keyword(s):  
Drug Interaction ◽  
Multiple Reaction Monitoring ◽  
Pharmacokinetic Interaction ◽  
Rat Plasma ◽  
Interaction Study ◽  
Triple Quadrupole Mass Spectrometer ◽  
Internal Standards ◽  
Spectrometric Data ◽  
Drug Drug Interaction

Background: Pantoprazole and atorvastatin are often used jointly in the clinic. The drug-drug interaction of pantoprazole and atorvastatin is worthy of being investigated. Objective: A highly rapid, sensitive, and selective LC-MS/MS method was developed for simultaneous quantification of pantoprazole and atorvastatin in rat plasma. Methods: Omeprazole and atorvastatin-d5 were used as the internal standards (ISs) of pantoprazole and atorvastatin, respectively. Simple protein precipitation was used to extract analytes from 50.0 μL plasma samples. Results: The chromatographic separation was achieved on a C18 column and the total chromatographic run time was 3.2 min. Acquisition of mass spectrometric data was performed on a triple-quadrupole mass spectrometer in multiple- reaction-monitoring (MRM) mode with an ESI source using the transition m/z 384→ 200 for pantoprazole and m/z 559.4→ 440.2 for atorvastatin, respectively. The method was validated over the concentration range of 20.0 ∼ 5000 ng/mL for pantoprazole and 1.00 ∼ 250 ng/mL for atorvastatin. All the validation results, including linearity, specificity, precision, accuracy, extraction recovery, matrix effect, and stability, met the acceptance criteria as per FDA guidelines. Conclusion: This method was successfully applied to a pharmacokinetic interaction study in Wistar rats. The results revealed significant evidence for the drug-drug interaction between pantoprazole and atorvastatin.

scholarly journals Extending Metabolomic Studies of Apis mellifera Venom: LC-MS-Based Targeted Analysis of Organic Acids

Toxins ◽  
2019 ◽  
Vol 12 (1) ◽  
pp. 14
Author(s):  
Magdalena Pawlak ◽  
Agnieszka Klupczynska ◽  
Zenon J Kokot ◽  
Jan Matysiak
Keyword(s):  
Citric Acid ◽  
Organic Acids ◽  
Kynurenic Acid ◽  
Glutaric Acid ◽  
Solid Phase ◽  
Multiple Reaction Monitoring ◽  
Dry Weight ◽  
Triple Quadrupole Mass Spectrometer ◽  
Targeted Analysis

Organic acids are important active small molecules present in venoms and toxins, which have not been fully explored yet. The aim of the study was the determination of organic acids in honeybee venom (HBV) samples by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two protocols for sample preparation were employed. A solid-phase extraction was used for the determination of malonic acid, fumaric acid, glutaric acid, and kynurenic acid. A dilute-and-shoot method was optimal for: citric acid, malic acid, and succinic acid. Chromatographic separation was performed using a Synergi Hydro-RP column. Detection was performed on a triple-quadrupole mass spectrometer operating in multiple reaction monitoring mode. Among the analytes, glutaric acid and kynurenic acid were present in HBV samples in the lowest concentrations, whereas citric acid was the most abundant acid in each sample, and accounted for an average of 86 mg/g (8.6%) of the venom dry weight. Organic acids were discussed in terms of function. This is the first study in the available literature that provides specific data on the content of organic acids in HBV using a validated quantitative method.

DBS Assay with LC-MS/MS for the Determination of Idelalisib, A Selective PI3K-δ Inhibitor in Mice Blood and Its Application to a Pharmacokinetic Study

Drug Research ◽  
2020 ◽  
Vol 71 (01) ◽  
pp. 36-42
Author(s):  
Harsha K. Tripathy ◽  
Nair S.V. Manju ◽  
Sreekanth Dittakavi ◽  
Ashok Zakkula ◽  
Ramesh Mullangi
Keyword(s):  
Pharmacokinetic Study ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Lymphocytic Leukemia ◽  
Extraction Solvent ◽  
Non Hodgkin Lymphoma ◽  
Validation Parameters ◽  
Multiple Reaction Monitoring Mode ◽  
Carry Over

AbstractIdelalisib is a selective and second-generation PI3K-δ inhibitor, approved for the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia. In this paper, we present a fully validated dried blood spot (DBS) method for the quantitation of idelalisib from mice blood using an LC-MS/MS, which was operated under multiple reaction monitoring mode. To the punched DBS discs, acidified methanol enriched with internal standard (IS; larotrectinib) was added and extracted using tert-butyl methyl ether as an extraction solvent with sonication. Chromatographic separation of idelalisib and the IS was achieved on an Atlantis dC18 column using a mixture of 10 mM ammonium formate:acetonitrile (25:75, v/v). The flow-rate and injection volume were 0.80 mL/min and 2.0 µL, respectively. Idelalisib and the IS were eluted at ~0.98 and 0.93 min, respectively and the total run time was 2.00 min. Idelalisib and the IS were analyzed using positive ion scan mode and parent-daughter mass to charge ion (m/z) transition of 416.1→176.1 and 429.1→342.1, respectively was used for the quantitation. The calibration range was 1.01−4 797 ng/mL. No matrix effect and carry over were observed. Haematocrit did not influence DBS idelalisib concentrations. All the validation parameters met the acceptance criteria. The applicability of the validated method was shown in a mice pharmacokinetic study.

scholarly journals Determination of Polypeptide Antibiotic Residues in Food of Animal Origin by Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3261
Author(s):  
Tomasz Bladek ◽  
Iwona Szymanek-Bany ◽  
Andrzej Posyniak
Keyword(s):  
High Performance ◽  
Multiple Reaction Monitoring ◽  
Gradient Elution ◽  
Animal Origin ◽  
Antibiotic Residues ◽  
Triple Quadrupole Mass Spectrometer ◽  
Limit Of Quantification ◽  
Food Of Animal Origin ◽  
Polypeptide Antibiotic

A novel UHPLC-MS/MS method for the determination of polypeptide antibiotic residues in animal muscle, milk, and eggs was developed and validated. Bacitracin A, colistin A, colistin B, polymyxin B1, and polymyxin B2 were extracted from the samples with a mixture of acetonitrile/water/ammonia solution 25%, 80/10/10 (v/v/v), and put through further evaporation, reconstitution, and filtration steps. The chromatographic separation was performed on a C18 column in gradient elution mode. Mass spectral acquisitions were performed in selective multiple reaction monitoring mode by a triple quadrupole mass spectrometer. The method was validated according to the criteria of Commission Decision 2002/657/EC. The method quantifies polypeptides in a linear range from 10 to 1000 μg kg−1, where the lowest concentration on the calibration curve refers to the limit of quantification (LOQ). The recoveries ranged from 70 to 99%, the repeatability was below 13%, and within-laboratory reproducibility was lower than 15%. The decision limit (CCα) and detection capability (CCβ) values were calculated, and ruggedness and stability studies were performed, to fulfill the criteria for confirmatory methods. Moreover, the developed method may also be used for screening purposes by its labor efficiency.

scholarly journals A RAPID AND SENSITIVE LIQUID CHROMATOGRAPHY- MASS SPECTROMETRY/MASS SPECTROMETRY METHOD FOR ESTIMATION OF PIOGLITAZONE, KETO PIOGLITAZONE AND HYDROXY PIOGLITAZONE IN HUMAN PLASMA

2017 ◽  
Vol 10 (12) ◽  
pp. 120
Author(s):  
Revathi Naga Lakshmi Ponnuri ◽  
Prahlad Pragallapati ◽  
Ravindra N ◽  
Venkata Basaveswara Rao Mandava
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Human Plasma ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Pharmacokinetic Parameters ◽  
Validation Parameters ◽  
Liquid Chromatography Tandem Mass ◽  
Multiple Reaction Monitoring Mode

  Objective: The main objective of the work was to develop a straightforward, fast and selective liquid chromatography/tandem mass spectrometry (LC-MS/MS) assay for determination of pioglitazone (PG), keto pioglitazone (KPG), and hydroxy pioglitazone (HPG) in human plasma and to validate as per recent guidelines.Methods: Analyte and the internal standard (IS) were extracted from plasma through liquid-liquid extraction and chromatographed on a Xterra RP18, 100×4.6, 5 μ column using methanol: acetonitrile mixture and 10 mM Ammonium formate buffer (70:30, v/v) as the mobile phase at a flow rate of 0.7 mL/min. The API-3200 Q Trap LC-MS/MS instrument in multiple reaction monitoring mode was used for detection. Diphenhydramine was utilized as IS.Results: The linearity was established in the concentration range of 20.15-1007.58 ng/mL for PG, 20.35-1017.58 ng/mL for KPG, and 19.68-491.22 ng/mL for HPG in human plasma. All the validation parameters were well within the acceptance limits.Conclusion: A new simple LC-MS/MS method was developed for the determination of PG, KPG, and HPG in human plasma. This method can be easily applied for the estimation of pharmacokinetic parameters of PG, KPG, and HPG.

scholarly journals High Throughput Quantitative Bioanalytical LC/MS/MS Determination of Gemifloxacin in Human Urine

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Adnan A. Kadi ◽  
Rihab F. Angawi ◽  
Mohamed W. Attwa ◽  
Hany W. Darwish ◽  
Ali Saber Abdelhameed
Keyword(s):  
Human Urine ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Urine Samples ◽  
Triple Quadrupole Mass Spectrometer ◽  
Mass Spectrometer System ◽  
The Mean ◽  
Syringe Filter ◽  
Spectrometer System

A highly specific, sensitive, and rapid method, to quantify gemifloxacin in human urine using HPLC coupled to the triple quadrupole mass spectrometer system, was developed and validated. Gemifloxacin and ofloxacin (internal standard) were rapidly extracted from urine samples without any tedious pretreatment procedure. Urine samples were filtered through a Millex-GP, 0.22 μm syringe filter. Optimal chromatographic separation of the analytes was achieved on Zorbax SB-C18(30 mm × 2 mm i.d., 3.5 μm maintained at ambient temperature). The mobile phase consisted of 0.1% formic acid (pH 3.2) and acetonitrile (80 : 20) and a flow rate of 0.2 mL min−1for 4 min. The analytes were monitored by electrospray ionization in positive ion multiple reaction monitoring mode. The method provided a linear response (r=0.9998) from a quantitation range of 5 ng mL−1to at least 500 ng mL−1. The mean extraction recovery % of gemifloxacin from spiked human urine was 101.33 ± 2.58%. The reproducibility of the method was reliable with the intra- and inter-day precision of <2% and accuracy within 2%. The established method was reliably applied for the determination of gemifloxacin in volunteers’ urine samples with the mean recoveries of gemifloxacin from Factive tablets 320 mg > 97.0%.

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