Laura Alksne, Svetlana Makarova, Jeļena Avsejenko, Alla Cibrovska, Julija Trofimova, Olga Valciņa
{"title":"Determination of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis by MALDI-TOF MS in clinical isolates from Latvia","authors":"Laura Alksne, Svetlana Makarova, Jeļena Avsejenko, Alla Cibrovska, Julija Trofimova, Olga Valciņa","doi":"10.1016/j.clinms.2020.03.001","DOIUrl":"10.1016/j.clinms.2020.03.001","url":null,"abstract":"<div><p>Rapid identification of methicillin-resistant <em>Staphylococcus</em> could ensure appropriate medical care. A total of 409 <em>Staphylococcus</em> spp. strains were used to develop a reliable MALDI-TOF method for species identification. We tested twelve <em>S. aureus</em> strains to compare three different sample preparation methods and the reproducibility of the methicillin-resistant <em>m</em>/<em>z</em> 2414 ± 2 indicator peak with direct method in triplicate. A total of 65 <em>Staphylococcus</em> spp. strains (including 37 methicillin-resistant strains) from clinical and hospital environment isolates were used to confirm the presence of phenol-soluble modulin (PSM-mec) peptide. All 272 <em>S. aureus</em> strains from 409 samples were correctly identified at species level by MALDI-TOF. The samples prepared by three methods gave spectra with differences in the intensities and presence of certain peaks. The PSM-mec peak was not visible after the extraction method. The peak <em>m</em>/<em>z</em> 2414 ± 2 was only detected in 61% of the methicillin-resistant strains and in none of the methicillin-sensitive strains. The peak reproducibility for the five analyzed <em>S. aureus</em> strains showing the peak at <em>m</em>/<em>z</em> 2414 ± 2 was 87%. The delta-toxin was observed in 49 out of 65 samples regardless of methicillin susceptibility, as well as in all the samples exhibiting the PSM-mec peak. The peak <em>m</em>/<em>z</em> 2414 ± 2 is specific to methicillin-resistant strains carrying the <em>mecA</em> gene, but the absence of peak <em>m</em>/<em>z</em> 2414 ± 2 does not exclude the possibility of resistance to methicillin. Thus, implementing MALDI-TOF analysis in routine laboratory work, especially with clinical samples, would in many cases provide rapid warning about the presence of methicillin-resistant strains.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2020.03.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39657087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A suggested standard for validation of LC-MS/MS based analytical series in diagnostic laboratories","authors":"Michael Vogeser , Judith A. Stone","doi":"10.1016/j.clinms.2020.02.002","DOIUrl":"10.1016/j.clinms.2020.02.002","url":null,"abstract":"","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2020.02.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39657085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katrin Gradl , Judith Taibon , Neeraj Singh , Eva Albrecht , Andrea Geistanger , Stephan Pongratz , Stefan Hutzler , Magdalena Mayer , Christine Kleinschmidt , Christian Geletneky , Verena Hofmann , Daniel Köppl , Manfred Rauh , Uwe Kobold
{"title":"An isotope dilution LC–MS/MS-based candidate reference method for the quantification of androstenedione in human serum and plasma","authors":"Katrin Gradl , Judith Taibon , Neeraj Singh , Eva Albrecht , Andrea Geistanger , Stephan Pongratz , Stefan Hutzler , Magdalena Mayer , Christine Kleinschmidt , Christian Geletneky , Verena Hofmann , Daniel Köppl , Manfred Rauh , Uwe Kobold","doi":"10.1016/j.clinms.2020.01.003","DOIUrl":"10.1016/j.clinms.2020.01.003","url":null,"abstract":"<div><p>The accurate measurement of androstenedione in human serum and plasma is required for steroid profiling to assure the appropriate diagnosis and differential diagnosis of hyperandrogenism. In this work, we introduce an isotope dilution liquid chromatography–tandem mass spectrometry (LC–MS/MS) candidate reference measurement procedure for the quantification of androstenedione in human serum and plasma. The performance of the procedure enables its use in the evaluation and standardization of routine assays and for the evaluation of patient samples to ensure the traceability of individual patient results. As the primary standard, a certified reference material from NMIA (National Measurement Institute, Australia) was used. Additionally, a quantitative nuclear magnetic resonance (qNMR) method was developed for the value assignment of the primary reference material, which ensures the direct traceability to SI units, as well as the independence from the availability of reference materials. <sup>13</sup>C<sub>3</sub>-labeled androstenedione was used as the internal standard. The introduced method allows the measurement of androstenedione in the range of 0.05–12 ng/mL, and the assay imprecision was found to be <2% between 5 and 12 ng/mL, 3.5% at 1.5 ng/mL, and 5.2% at 0.05 ng/mL, with an accuracy of 95–105% for the serum and 91–103% for the plasma matrix. The transferability to a second laboratory was validated by method comparison based on 112 patient samples. The comparison of the results obtained from the presented method and an LC–MS/MS routine assay, using 150 native patient samples, showed a good correlation with a bias of the routine method of ≤4.0%.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2020.01.003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39657083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quantification of volatile metabolites in exhaled breath by selected ion flow tube mass spectrometry, SIFT-MS","authors":"Patrik Španěl, David Smith","doi":"10.1016/j.clinms.2020.02.001","DOIUrl":"10.1016/j.clinms.2020.02.001","url":null,"abstract":"<div><p>Selected ion flow tube mass spectrometry, SIFT-MS, is a non-separative method for direct quantitative analyses of volatile compounds, VOCs, in air and humid breath based on chemical ionization. Selected reagent ions, either H<sub>3</sub>O<sup>+</sup>, NO<sup>+</sup> or O<sub>2</sub><sup>+</sup> (non-reactive with major components of air), ionize analyte molecules during a defined time in a flow tube by ion-molecule reactions thus producing analyte ions that are characteristic of the neutral analyte VOCs. Concentrations can be calculated in real-time from the ion count rates. Direct on-line analysis of single or multiple breath exhalations or off-line analysis of breath samples collected into bags can be performed. Several volatile breath metabolites have been quantified by SIFT-MS, including ammonia, acetone, hydrogen cyanide, alcohols, pentane, acetic acid, methane, and sulphur compounds. Their potential as biomarkers is discussed.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2020.02.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39657086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development and validation of a liquid chromatography-tandem mass spectrometry method for determination of ibuprofen in human plasma","authors":"Apichaya Puangpetch , Anchalee Limrungsikul , Santirhat Prommas , Pattarawit Rukthong , Chonlaphat Sukasem","doi":"10.1016/j.clinms.2019.10.002","DOIUrl":"10.1016/j.clinms.2019.10.002","url":null,"abstract":"<div><p>Ibuprofen is widely used to reduce fever, pain, and inflammation and in the treatment of patent ductus arteriosus (PDA) in preterm infants. However, to study the impact of pharmacokinetics of ibuprofen on the rate of ductus arteriosus closure in humans, a quantitative method is required. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a highly sensitive, accurate, reliable, fast, and simple bioanalytical method. In this study, we developed and utilized an LC-MS/MS method to determine ibuprofen bioavailability. One of the novel aspects of this work is the small specimen volume required for the analysis (i.e., 50 µL). The calibration curve was linear across a concentration range of 0.15–50 μg/mL. The coefficient of variation for intra-day and inter-day precision was within 0.78%–7.21% and accuracy was within 97.52%–107.21% of the nominal values for low, medium, and high quality control (QC) concentration levels—QCL, QCM, and QCH (0.45, 9.0, and 40.0 μg/mL, respectively). For ibuprofen concentrations at the lower limit of quantitation (LLOQ), intra-day and inter-day accuracy were 98.11% and 99.81%, respectively; however, the intra-day and inter-day precision were 1.89% and 5.37%, respectively. The pharmacokinetic study involved 18 neonatal subjects who were grouped into low- or high-dose ibuprofen groups. The median maximum concentration for low- and high-dose regimens were 16.05 (14.21–19.32) and 24.10 (20.63–32.03) µg/mL, respectively, and the median elimination rate constant was 0.041 (0.026–0.047) and 0.071 (0.050–0.073) h<sup>−1</sup>, respectively. Thus, the fully validated LC-MS/MS method was determined to be suitable for analyzing unknown plasma samples for ibuprofen pharmacokinetic, bioavailability, and bioequivalence studies.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2019.10.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80401592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lisa M. Johnson, Anthony A. Killeen, Jesse C. Seegmiller
{"title":"Development of a LC-MS/MS method for urinary hydroxytyrosol as a marker for consumption of olive oil","authors":"Lisa M. Johnson, Anthony A. Killeen, Jesse C. Seegmiller","doi":"10.1016/j.clinms.2019.10.001","DOIUrl":"10.1016/j.clinms.2019.10.001","url":null,"abstract":"<div><p>The aim of this study was to develop and validate a LC-MS/MS method to quantitate hydroxytyrosol in urine for clinical studies to monitor compliance of consumption of dietary extra virgin olive oil. Both pre-analytical and analytical issues were examined. The stability of hydroxytyrosol was monitored in both urine and synthetic urine at four different temperatures (room temperature, 4 °C, −20 °C, or −80 °C) for four weeks either with or without the additive acetic acid. The LC-MS/MS method was validated by performing linearity, imprecision, recovery, and carryover studies.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2019.10.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78222510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher M. Shuford , Jay S. Johnson , J. Will Thompson , Patricia L. Holland , Andrew N. Hoofnagle , Russell P. Grant
{"title":"More sensitivity is always better: Measuring sub-clinical levels of serum thyroglobulin on a µLC–MS/MS system","authors":"Christopher M. Shuford , Jay S. Johnson , J. Will Thompson , Patricia L. Holland , Andrew N. Hoofnagle , Russell P. Grant","doi":"10.1016/j.clinms.2020.01.001","DOIUrl":"10.1016/j.clinms.2020.01.001","url":null,"abstract":"<div><p>Although liquid chromatography–tandem mass spectrometry (LC–MS/MS) assays for thyroglobulin (Tg) are resistant to autoantibody (TgAb) interference, recent studies have demonstrated approximately 40% of TgAb-positive individuals with recurrent thyroid cancer have Tg concentrations below the lower limit of quantification (LLOQ) of the LC–MS/MS assays described to date (i.e., <0.5 ng/mL), resulting in false-negative findings during post-thyroidectomy monitoring. To reduce false negative results due to insufficient analytical sensitivity, a new Tg assay was developed on a commercially available LC–MS/MS system operating at microliter/minute flow-rates (i.e., µLC–MS/MS) to maximize the analytical sensitivity and achieve a LLOQ of 0.02 ng/mL. When applied to the measurement of TgAb-negative and TgAb-positive patient serum samples previously measuring below the LLOQ of current immunometric and LC–MS/MS assays (LLOQ, 0.1–0.2 ng/mL), concentrations were measurable by µLC–MS/MS in 66% and 44% of samples, respectively – possibly explaining the persistence of TgAb in those patients. Patients with low Tg concentrations measured by µLC–MS/MS (<0.1 ng/mL) also exhibited elevation in their Tg concentrations upon hormone stimulation, indicating the detected Tg was produced from remnant thyroid tissue and would be suitable as a tissue biomarker. Forty-eight TgAb-positive patient specimens with undetectable Tg by both conventional LC–MS/MS (<0.15 ng/mL) and immunometric (<0.1 ng/mL) assays demonstrated measureable Tg concentrations by the new µLC–MS/MS assay in approximately one-third of the specimens, despite all patients being disease free at the time of collection, suggesting interference-free monitoring of low Tg levels may be feasible prior to the on-set of recurrent disease using a sensitive LC–MS/MS assay.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2020.01.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39657082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Medical mass spectrometrist (MMS) training and certification: A key step to expanding routine clinical mass spectrometry usage in Japan","authors":"Fumio Nomura , Toyofumi Nakanishi , Kazuo Igarashi , Seiji Yamaguchi , Mitsutoshi Setou , Toshimitsu Niwa","doi":"10.1016/j.clinms.2019.11.001","DOIUrl":"10.1016/j.clinms.2019.11.001","url":null,"abstract":"<div><p>Mass spectrometry (MS) is increasingly used in clinical medicine in Japan. In contrast to the successful application of MS in clinical microbiology, the adoption of MS-based assays for routine testing in clinical chemistry is very slow. In order to promote the significant benefits that MS platforms bring to laboratory medicine and patient care, the Japanese Society for Biomedical Mass Spectrometry (JSBMS) initiated a medical mass spectrometrist (MMS) certification program in 2013. As of Dec 2018, 308 persons from various medical specialties have been certified. We believe that they will play significant roles for expanding routine clinical MS usage in Japan.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2019.11.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85049349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of mass spectrometry in establishing safety and efficacy of botanical dietary supplements","authors":"Richard B. van Breemen","doi":"10.1016/j.clinms.2019.12.001","DOIUrl":"10.1016/j.clinms.2019.12.001","url":null,"abstract":"<div><p>As in drug discovery and development, mass spectrometry has become essential at all stages for establishing the safety and efficacy of botanical dietary supplements. Applications of mass spectrometry to the development of botanical dietary supplements include preclinical studies of the mechanisms of action (<em>e.g</em>., proteomic target identification and validation); identification of active natural products using high resolution tandem mass spectrometry; chemical standardization using UHPLC-MS/MS; and studies of metabolism, absorption and toxicity of active compounds using high resolution and UHPLC-MS/MS. Clinical applications of mass spectrometry include evaluation of the potential for drug-botanical interactions; investigation of the pharmacokinetics of active compounds; and quantitative analysis of biomarkers of efficacy during Phase I and II and clinical trials of safety and efficacy of botanical dietary supplements.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2019.12.001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37809847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tandem mass spectrometry in the clinical laboratory: A tutorial overview","authors":"J. Grace van der Gugten","doi":"10.1016/j.clinms.2019.09.002","DOIUrl":"10.1016/j.clinms.2019.09.002","url":null,"abstract":"<div><p>Tandem mass spectrometry (tandem MS) is a powerful technique that directly measures compounds based on their molecular weight. Liquid chromatography triple quadrupole mass spectrometry (LC-MS/MS), a type of tandem MS, has been increasingly adopted by clinical laboratories in recent years. While it is complicated and challenging, it has selectivity and accuracy advantages over more traditional laboratory techniques such as immunoassay. Able to measure a wide range of compounds, when correctly utilized and implemented, LC-MS/MS can benefit the clinical laboratory and improve patient care. This mini review is an introduction to clinical LC-MS/MS for the novice user.</p></div>","PeriodicalId":48565,"journal":{"name":"Clinical Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":2.1,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.clinms.2019.09.002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85642778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}