scholarly journals Quantitative mass spectrometry imaging of drugs and metabolites: a multiplatform comparison

2021 ◽  
Vol 413 (10) ◽  
pp. 2779-2791
Author(s):  
Lieke Lamont ◽  
Darya Hadavi ◽  
Brent Viehmann ◽  
Bryn Flinders ◽  
Ron M. A. Heeren ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Standard Deviation ◽  
Relative Standard Deviation ◽  
Mass Spectrometry Imaging ◽  
Pharmaceutical Compounds ◽  
Quantitative Mass Spectrometry ◽  
Tissue Model ◽  
Drug Candidates ◽  
Relative Standard ◽  
3D Printed

AbstractMass spectrometry imaging (MSI) provides insight into the molecular distribution of a broad range of compounds and, therefore, is frequently applied in the pharmaceutical industry. Pharmacokinetic and toxicological studies deploy MSI to localize potential drugs and their metabolites in biological tissues but currently require other analytical tools to quantify these pharmaceutical compounds in the same tissues. Quantitative mass spectrometry imaging (Q-MSI) is a field with challenges due to the high biological variability in samples combined with the limited sample cleanup and separation strategies available prior to MSI. In consequence, more selectivity in MSI instruments is required. This can be provided by multiple reaction monitoring (MRM) which uses specific precursor ion-product ion transitions. This targeted approach is in particular suitable for pharmaceutical compounds because their molecular identity is known prior to analysis. In this work, we compared different analytical platforms to assess the performance of MRM detection compared to other MS instruments/MS modes used in a Q-MSI workflow for two drug candidates (A and B). Limit of detection (LOD), linearity, and precision and accuracy of high and low quality control (QC) samples were compared between MS instruments/modes. MRM mode on a triple quadrupole mass spectrometer (QqQ) provided the best overall performance with the following results for compounds A and B: LOD 35.5 and 2.5 μg/g tissue, R2 0.97 and 0.98 linearity, relative standard deviation QC <13.6%, and 97–112% accuracy. Other MS modes resulted in LOD 6.7–569.4 and 2.6–119.1 μg/g tissue, R2 0.86–0.98 and 0.86–0.98 linearity, relative standard deviation QC < 19.4 and < 37.5%, and 70–356% and 64–398% accuracy for drug candidates A and B, respectively. In addition, we propose an optimized 3D printed mimetic tissue model to increase the overall analytical throughput of our approach for large animal studies. The MRM imaging platform was applied as proof-of-principle for quantitative detection of drug candidates A and B in four dog livers and compared to LC-MS. The Q-MSI concentrations differed <3.5 times with the concentrations observed by LC-MS. Our presented MRM-based Q-MSI approach provides a more selective and high-throughput analytical platform due to MRM specificity combined with an optimized 3D printed mimetic tissue model. Graphical abstract

scholarly journals Liquid Chromatographic Determination of Ampicillin Residues in Porcine Muscle Tissue by a Multipenicillin Analytical Method: European Collaborative Study

2002 ◽  
Vol 85 (4) ◽  
pp. 889-900 ◽  
Author(s):  
Eric Verdon ◽  
Pierric Couëdor ◽  
Pierre Maris ◽  
Michel Laurentie ◽  
P Batjoens ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Standard Deviation ◽  
Relative Standard Deviation ◽  
Muscle Tissue ◽  
Phosphate Buffer ◽  
Collaborative Study ◽  
Porcine Muscle ◽  
Relative Standard ◽  
Liquid Chromatographic

Abstract A collaborative study involving 14 laboratories was conducted to determine residues of ampicillin in porcine muscle tissue by using a liquid chromatographic method developed for multipenicillin analysis that can quantitate 8 penicillin compounds (benzylpenicillin, phenoxymethylpenicillin, ampicillin, amoxicillin, nafcillin, oxacillin, cloxacillin, and dicloxacillin) at trace levels in muscle tissue. This method involves extraction of the penicillins with phosphate buffer, pH 9, followed cleanup and concentration on a C18 solid-phase extraction column and reaction with benzoic anhydride at 50°C and with 1,2,4-triazole and mercury(II) chloride solution, pH 9.0, at 65°C. The derivatized compounds are eluted isocratically on a C8 column with a mobile phase of acetonitrile and phosphate buffer (pH 6; 0.1M) containing sodium thiosulfate and the ion-pair reagent tetrabutylammonium hydrogen sulfate. The penicillins are detected by UV absorption at 325 nm. The limit of detection and the limit of determination (quantitation) of the method were calculated to be approximately 3–5 and 25 μg/kg, respectively, in accordance with the criteria of European Union (EU) Decision No. 93/256/EEC. In this first interlaboratory study, collaborators were instructed to monitor 4 different penicillin compounds (benzylpenicillin, phenoxymethylpenicillin, ampicillin, and amoxicillin) by analyzing 8 blind samples of muscle tissue in triplicate. These samples were prepared from 2 materials containing different concentrations of incurred ampicillin (63.5 μg/kg for material No. 1 and 358.1 μg/kg for material No. 2) and 1 blank material. The repeatability relative standard deviation and the reproducibility relative standard deviation were 10.2 and 17.4%, respectively, for material No. 1 and 7.0 and 16.0%, respectively, for material No. 2. These results demonstrate that the method is suitable for the determination of ampicillin residues in muscle tissue at the EU maximum residue limit (50 μg/kg) and above. However, the identification of positives by this procedure may need additional confirmation by techniques with greater specificity, such as liquid chromatography combined with mass spectrometry, or tandem mass spectrometry. Investigations regarding the basis of interlaboratory testing studies will further demonstrate the suitability of multiresidue methodology for detecting and quantitating other compounds in the family of penicillin antibiotics.

scholarly journals Determination of Pesticide Residues in Nonfatty Fooda by Percritical Extraction aqnd Gas Chromatography/Mass Spectrometry: Collaborative Study

2002 ◽  
Vol 85 (5) ◽  
pp. 1148-1166 ◽  
Author(s):  
Steven J Lehotay ◽  
A Schaner ◽  
S Nemoto ◽  
J Harman-Fetcho ◽  
J Barney ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Standard Deviation ◽  
Relative Standard Deviation ◽  
Pesticide Residues ◽  
Collaborative Study ◽  
Green Bean ◽  
Gas Chromatography Mass Spectrometry ◽  
Chromatography Mass Spectrometry ◽  
Relative Standard

Abstract A collaborative study was conducted to determine multiple pesticide residues in apple, green bean, and carrot by using supercritical fluid extraction(SFE) and gas chromatography/mass spectrometry(GC/MS). Seventeen laboratories from 7 countries participated in the final study, and a variety of different instruments was used by collaborators. The procedure simply entails 3 steps: (1) mix 1.1 g drying agent (Hydromatrix) per 1 g frozen precomminuted sample, and load 4–5.5 g of this mixture into a 7–10 mL extraction vessel; (2) perform SFE for 20–30 min with a 1–2 mL/min flow rate of carbon dioxide at 0.85 g/mL density (320 atm, 60°C); and (3) inject the extract, which was collected on a solid–phase or in a liquid trap, into the gas chromatograph/mass spectrometer, using either an ion-trap instrument in full-scan mode or a quadrupole-type instrument in selected-ion monitoring mode. The ability of GC/MS to simultaneously quantitate and confirm the identity of the semivolatile analytes at trace concentrations is a strong feature of the approach. The selectivity of SFE and GC/MS avoids the need for post-extraction cleanup steps, and the conversion of the CO2 solvent to a gas after SFE eliminates the solvent evaporation step common in traditional methods. The approach has several advantages, but its main drawback is the lower recoveries for the most polar analytes, such as methamidophos and acephate, and the most nonpolar analytes, such as pyrethroids. Recoveries for most pesticides are &gt;75%, and recoveries of nonpolar analytes are still &gt;50%. The(within-laboratory) repeatability relative standard deviation (RSDr) values of the recoveries are generally &lt;15%. More specifically, the average results from the 9–14 laboratories in the final analysis of 6 blind duplicates at 3 concentrations for each pesticide are as follows: carbofuran in apple (75–500 ng/g), 89% recovery, 7% RSDr, 9% reproducibility relative standard deviation (RSDR); diazinon in apple (60–400 ng/g), 83% recovery, 13% RSDr, 17% RSDMR; vinclozolin in apple (6–400 ng/g), 97% recovery, 13% RSDr, 18% RSDR; chlorpyrifos in apple (50–300 ng/g), 105% recovery, 11% RSDr, 13% RSDR; endosulfan sulfate in apple (150–1000 ng/g), 95% recovery, 15% RSDr, 17% RSDR; trifluralin in green bean (30–200 ng/g), 58% recovery, 11% RSDr, 27% RSDR; dacthal in green bean (60–400 ng/g), 88% recovery, 11% RSDr, 17% RSDR; quintozene in green bean (60–400 ng/g), 79% recovery, 13% RSDr, 18% RSDR; chlorpyrifos in green bean (50–300 ng/g), 84% recovery, 11% RSDr, 17% RSDR; p,p′ -DDE in green bean (45–300 ng/g), 64% recovery, 14% RSDr, 27% RSDR; atrazine in carrot (75–500 ng/g), 90% recovery, 11% RSDr, 15% RSDR; metalaxyl in carrot (75–500 ng/g), 89% recovery, 8% RSDr, 12% RSDR; parathion–methyl in carrot (75–500 ng/g), 84% recovery, 14% RSDr, 15% RSDR; chlorpyrifos in carrot (50–300 ng/g), 77% recovery, 13% RSDr, 19% RSDR; and bifenthrin in carrot (90–600 ng/g), 63% recovery, 12% RSDr, and 25% RSDR. All analytes except for the nonpolar compound strifluralin, p,p′ -DDE, and bifenthrin gave average Horwitz ratios of &lt;1.0 when AOAC criteria were used. These 3 analytes had high RSDr values but lower RSDR values, which indicated that certainSFE instruments gave consistently lower recoveries for nonpolar compounds. The collaborative study results demonstrate that the method meets the purpose of many monitoring programs for pesticide residue analysis, and the Study Director recommends that it be adopted Official

scholarly journals Method Validation for Determination of Alkaloid Content in Goldenseal Root Powder

2003 ◽  
Vol 86 (3) ◽  
pp. 476-483 ◽  
Author(s):  
Holly A Weber ◽  
Matthew K Zart ◽  
Andrew E Hodges ◽  
Kellie D White ◽  
Sarah M Barnes ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Standard Deviation ◽  
Relative Standard Deviation ◽  
Analytical Method ◽  
Hydrastis Canadensis ◽  
Extraction Solvent ◽  
Relative Standard ◽  
Oregon Grape

Abstract A fast, practical ambient extraction methodology followed by isocratic liquid chromatography (LC) analysis with UV detection was validated for the determination of berberine, hydrastine, and canadine in goldenseal (Hydrastis canadensis L.) root powder. The method was also validated for palmatine, a major alkaloid present in the possible bioadulterants Coptis, Oregon grape root, and bar-berry bark. Alkaloid standard solutions were linear over the evaluated concentration ranges. The analytical method was linear for alkaloid extraction using 0.3–2 g goldenseal root powder/100 mL extraction solvent. Precision of the method was demonstrated using 10 replicate extractions of 0.5 g goldenseal root powder, with percent relative standard deviation for all 4 alkaloids ≤1.6. Alkaloid recovery was determined by spiking each alkaloid into triplicate aliquots of neat goldenseal root powder. Recoveries ranged from 92.3% for palmatine to 101.9% for hydrastine. Ruggedness of the method was evaluated by performing multiple analyses of goldenseal root powder from 3 suppliers over a 2-year period. The method was also used to analyze Coptis root, Oregon grape root, barberry bark, and celandine herb, which are possible goldenseal bioadulterants. The resulting chromato-graphic profiles of the bioadulterants were significantly different from that of goldenseal. The method was directly transferred to LC with mass spectrometry, which was used to confirm the presence of goldenseal alkaloids tetrahydro-berberastine, berberastine, canadaline, berberine, hydrastine, and canadine, as well as alkaloids from the bioadulterants, including palmatine, jatrorrhizine, and coptisine.

Simultaneous Determination of Nonylphenol and Short-Chain Nonylphenol Polyeothoxylates by Gas Chromatography Coupled to Mass Spectrometry

2010 ◽  
Vol 178 ◽  
pp. 361-366
Author(s):  
Yu Shuang Qiao
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Standard Deviation ◽  
Simultaneous Determination ◽  
Relative Standard Deviation ◽  
Ultrasonic Extraction ◽  
Short Chain ◽  
Good Separation ◽  
Relative Standard

This paper presents a method for the simultaneous determinat of NP and NPEO1-2 using GC-MS in sludge samples. using ultrasonic extraction, derivatization techniques, the results show that good separation of three substances, a well-shaped peak can be observed on every selected ion chromatogram. the ultrasonic extraction recoveries ranged from 80% to 102% , the instrumental limits of detection for these compounds were 2 ng/g、2 ng/g and 1.5 ng/g and the relative standard deviation(RSD) was below 15%. The establishment of this method provided the method safeguard for the control of NP and NPEO1-2 in sludge samples.

An Automated Procedure for the Determination of Ammonia in Tobacco

1972 ◽  
Vol 6 (4) ◽  
Author(s):  
P.F. Collins ◽  
W.W. Lawrence ◽  
J.F. Williams
Keyword(s):  
Standard Deviation ◽  
Relative Standard Deviation ◽  
Distillation Method ◽  
Relative Standard ◽  
Tobacco Sample ◽  
Automated Determination

AbstractA procedure for the automated determination of ammonia in tobacco has been developed. Ammonia is extracted from the ground tobacco sample with water and is determined with a Technicon Auto Analyser system which employs separation of the ammonia through volatilization followed by colourimetry using the phenate-hypochlorite reaction. The procedure has been applied to a variety of tobaccos containing from 0.02 to 0.5 % ammonia with an overall relative standard deviation of 2 %. The accuracy of the procedure as judged by recovery tests and by comparison to a manual distillation method is considered adequate

How Certain Are the Reported Ionic Conductivities of Thiophosphate-Based Solid Electrolytes? an Interlaboratory Study

2020 ◽  
Author(s):  
Saneyuki Ohno ◽  
Tim Bernges ◽  
Johannes Buchheim ◽  
Marc Duchardt ◽  
Anna-Katharina Hatz ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Ionic Conductivity ◽  
Relative Standard Deviation ◽  
Solid Electrolytes ◽  
Ionic Conductivities ◽  
Ionic Conductors ◽  
Energy Storage Devices ◽  
Activation Barriers ◽  
Storage Devices ◽  
Relative Standard

<p>Owing to highly conductive solid ionic conductors, all-solid-state batteries attract significant attention as promising next-generation energy storage devices. A lot of research is invested in the search and optimization of solid electrolytes with higher ionic conductivity. However, a systematic study of an <i>interlaboratory reproducibility</i> of measured ionic conductivities and activation energies is missing, making the comparison of absolute values in literature challenging. In this study, we perform an uncertainty evaluation via a Round Robin approach using different Li-argyrodites exhibiting orders of magnitude different ionic conductivities as reference materials. Identical samples are distributed to different research laboratories and the conductivities and activation barriers are measured by impedance spectroscopy. The results show large ranges of up to 4.5 mScm<sup>-1</sup> in the measured total ionic conductivity (1.3 – 5.8 mScm<sup>-1</sup> for the highest conducting sample, relative standard deviation 35 – 50% across all samples) and up to 128 meV for the activation barriers (198 – 326 meV, relative standard deviation 5 – 15%, across all samples), presenting the necessity of a more rigorous methodology including further collaborations within the community and multiplicate measurements.</p>

scholarly journals Indirect and Direct Determination of the Casein Content of Milk by Kjeldahl Nitrogen Analysis: Collaborative Study

1998 ◽  
Vol 81 (4) ◽  
pp. 763-774 ◽  
Author(s):  
Joanna M Lynch ◽  
David M Barbano ◽  
J Richard Fleming
Keyword(s):  
Standard Deviation ◽  
Nitrogen Content ◽  
Relative Standard Deviation ◽  
Collaborative Study ◽  
Direct Determination ◽  
Raw Milk ◽  
Method Performance ◽  
Relative Standard ◽  
Milk Casein

Abstract The classic method for determination of milk casein is based on precipitation of casein at pH 4.6. Precipitated milk casein is removed by filtration and the nitrogen content of either the precipitate (direct casein method) or filtrate (noncasein nitrogen; NCN) is determined by Kjeldahl analysis. For the indirect casein method, milk total nitrogen (TN; Method 991.20) is also determined and casein is calculated as TN minus NCN. Ten laboratories tested 9 pairs of blind duplicate raw milk materials with a casein range of 2.42- 3.05℅ by both the direct and indirect casein methods. Statistical performance expressed in protein equivalents (nitrogen ⨯ 6.38) with invalid and outlier data removed was as follows: NCN method (wt%), mean = 0.762, sr = 0.010, SR = 0.016, repeatability relative standard deviation (RSDr) = 1.287℅, reproducibility relative standard deviation (RSDR) = 2.146%; indirect casein method (wt℅), mean = 2.585, repeatability = 0.015, reproducibility = 0.022, RSDr = 0.560℅, RSDR = 0.841; direct casein method (wt℅), mean = 2.575, sr = 0.015, sR = 0.025, RSDr = 0.597℅, RSDR = 0.988℅. Method performance was acceptable and comparable to similar Kjeldahl methods for determining nitrogen content of milk (Methods 991.20, 991.21,991.22, 991.23). The direct casein, indirect casein, and noncasein nitrogen methods have been adopted by AOAC INTERNATIONAL.

scholarly journals A computer-controlled potentiometric/spectrophotometric titrator

1988 ◽  
Vol 10 (2) ◽  
pp. 95-100
Author(s):  
John D. Stong
Keyword(s):  
Standard Deviation ◽  
Relative Standard Deviation ◽  
Bromophenol Blue ◽  
System Control ◽  
Data Format ◽  
Relative Standard ◽  
Spectrophotometric Titrations ◽  
Computer Controlled ◽  
Major Attention ◽  
Diode Array Spectrophotometer

A laboratory computer controlled potentiometric titrator interfaced to a diode array spectrophotometer is described. The titrator consists of widely used, commercially available components; therefore, major attention is given to modes of interconnection and software implementation in data format and system control. Replicate potentiometric titrations of glycines gave a relative standard deviation in titre of 1.035% and a relative standard deviation in pH of 0.745%. Replicate spectrophotometric titrations of bromophenol blue were analysed at three wavelengths to yield pKa= 3.898 ± 0.075 (1.9% rsd).Methods of data presentation and manipulation are presented.

Sign in / Sign up

Export Citation Format

Share Document