Journal of Mass Spectrometry and Advances in the Clinical Lab最新文献

{"title":"Corrigendum to “Development and validation of a multiplexed LC-MS/MS ketone body assay for clinical diagnostics” [J. Mass Spectrom. Adv. Clin. Lab 31 (2024) 49–58]","authors":"Robin H.J. Kemperman , Rebecca D. Ganetzky , Stephen R. Master","doi":"10.1016/j.jmsacl.2024.07.001","DOIUrl":"10.1016/j.jmsacl.2024.07.001","url":null,"abstract":"","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"33 ","pages":"Page 21"},"PeriodicalIF":3.1,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X24000245/pdfft?md5=c80fa893a526595043289ead76e5c45e&pid=1-s2.0-S2667145X24000245-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141639424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Despite the improved clinical sensitivity of the Roche benzodiazepines II assay it cannot replace mass spectrometry in all patient populations","authors":"Nicole V. Tolan ,&nbsp;Sacha Uljon ,&nbsp;M. Lauren Donnelly-Morell ,&nbsp;Melissa Zhao ,&nbsp;Grace K. Mahowald ,&nbsp;Marion L. Snyder ,&nbsp;Lindsey Contella ,&nbsp;Elizabeth D. Urwiller ,&nbsp;Maria Daluz Fernandes ,&nbsp;Phillip Kang ,&nbsp;Stacy E.F. Melanson","doi":"10.1016/j.jmsacl.2024.06.002","DOIUrl":"https://doi.org/10.1016/j.jmsacl.2024.06.002","url":null,"abstract":"<div><h3>Introduction</h3><p>Benzodiazepines are frequently prescribed and misused therefore urine drug screening (UDS) is performed in many patient populations. Most current benzodiazepine immunoassays have poor sensitivity, particularly for detecting the metabolites of newer benzodiazepines such as lorazepam in urine.</p></div><div><h3>Objectives</h3><p>We aimed to verify the clinical performance of the new qualitative Roche Benzodiazepines II (BNZ2) immunoassay, as well as compare its performance to the Roche Benzodiazepines Plus (BENZ) assay in two patient populations: UDS in the emergency department (ED) and compliance monitoring.</p></div><div><h3>Methods</h3><p>An initial verification study was performed, selecting for samples containing clonazepam and lorazepam metabolites. Performance of the BNZ2 and BENZ assays was compared to liquid chromatography-tandem mass spectrometry (LC-MS/MS) as the reference method. Sensitivity, specificity, false positive rate (FPR) and false negative rate (FNR) were determined.</p></div><div><h3>Results</h3><p>We verified the performance claims in the initial verification and demonstrated similar precision, with coefficient of variations (CVs) of 12.8% and 7.7% for negative and positive controls, respectively. Furthermore, we observed higher clinical sensitivity and lower FNR with the BNZ2 assay in both the ED and compliance monitoring populations due to improved cross-reactivity for lorazepam and clonazepam metabolites. Despite these improvements, the BNZ2 assay was unable to detect 27% of specimens positive by LC-MS/MS, including specimens from patients using benzodiazepines without prescription.</p></div><div><h3>Discussion</h3><p>Due to its improved performance and rapid turnaround time, the BNZ2 assay should be implemented for UDS in the ED. However, the assay should not replace LC-MS/MS testing for compliance monitoring, as unsuspected benzodiazepine use may go undetected.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"33 ","pages":"Pages 14-20"},"PeriodicalIF":3.1,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X24000233/pdfft?md5=52e2c37dabd93cf130367c283b244361&pid=1-s2.0-S2667145X24000233-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141485856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic drug monitoring of mycophenolic acid and azole antifungals on two distinct LC-MS/MS instruments","authors":"Jill K. Wolken ,&nbsp;Wenjing Cao ,&nbsp;Min Cui ,&nbsp;Zhicheng Jin","doi":"10.1016/j.jmsacl.2024.06.001","DOIUrl":"https://doi.org/10.1016/j.jmsacl.2024.06.001","url":null,"abstract":"<div><h3>Background</h3><p>As an active metabolite of a commonly prescribed immunosuppressant, mycophenolic acid (MPA) levels are often monitored to prevent organ rejection following a transplant. Triazoles are often prescribed for treatment of invasive fungal infections in immunocompromised patients. Due to the variability in individual pharmacokinetics and drug-drug interactions, therapeutic drug monitoring is recommended for triazole antifungals. A multiplex LC-MS/MS assay has been developed that can quantify both MPA and triazole drugs in serum.</p></div><div><h3>Methods</h3><p>A sample preparation procedure was established to spike in internal standard compounds and precipitate proteins. Reversed-phase chromatographic separation was performed on a C18 column with an analysis time of five minutes per sample. The mass spectrometer was operated in multiple reaction monitoring mode. The method was validated on two HPLC systems interfaced with either a Triple Quad 6500 or an API 4000 instrument.</p></div><div><h3>Results</h3><p>The multiplex assay was linear over a wide dynamic range with analyte measurable ranges of 0.4–48 μg/mL for MPA, 0.1–12 μg/mL for posaconazole, and 0.2–24 μg/mL for voriconazole, itraconazole, hydroxyitraconazole, and isavuconazole. The between-day and intraday imprecisions were less than 10 %. Limits of detection were below 0.04 ug/mL with limits of quantitation below 0.2 μg/mL. Method comparison studies against the current in-house method met acceptance criteria. The instrument comparison study demonstrated a strong correlation between data collected from the two systems.</p></div><div><h3>Conclusion</h3><p>A robust multiplex LC-MS/MS assay was developed and validated for monitoring MPA and triazoles drug levels in a clinical laboratory. The assay performance on two distinct instruments was acceptable and comparable.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"33 ","pages":"Pages 7-13"},"PeriodicalIF":2.2,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X24000221/pdfft?md5=4e88c1d54e719b4e4bd35ea01d758b56&pid=1-s2.0-S2667145X24000221-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141326091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spuriously low immunosuppressant results due to incomplete hemolysis – A pitfall in transplant patient therapeutic drug monitoring","authors":"Michael Vogeser,&nbsp;Katharina Habler","doi":"10.1016/j.jmsacl.2024.05.002","DOIUrl":"10.1016/j.jmsacl.2024.05.002","url":null,"abstract":"<div><h3>Objective</h3><p>Therapeutic drug monitoring (TDM) plays a crucial role in transplantation medicine when it comes to immunosuppressants like Tacrolimus, Cyclosporine A, Sirolimus, and Everolimus. The analysis involves using immunometric or mass spectrometric methods on whole blood samples. Hemolysis of the samples is necessary for the assessment. Typically, this is accomplished through manual protein precipitation using pre-treatment reagents, followed by vigorous vortex mixing and subsequent centrifugation. It is important to note that omitting the vortex step in these manual procedures can be seen as a potential procedural error.</p></div><div><h3>Methods</h3><p>To assess the potential impact of omitting the vortex step, an experiment was conducted. Clinical samples were divided into two aliquots, which were then analyzed comparatively. In one group of aliquots, the vortex step was intentionally omitted, while the other followed the correct execution of the test.</p></div><div><h3>Results</h3><p>The non-vortex-mixed samples showed significantly erroneous low results for all analytes.</p></div><div><h3>Conclusion</h3><p>Omitting or inadequately performing vortex mixing during the hemolysis procedure can be considered as a significant potential source of analytical error in TDM of immunosuppressants.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"33 ","pages":"Pages 4-6"},"PeriodicalIF":2.2,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X2400021X/pdfft?md5=7c32ba18f8efa0cf90c8496e47976088&pid=1-s2.0-S2667145X2400021X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141038238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surreptitious pipetting errors on a vendor-programmed liquid handler","authors":"Kelly Britt-Rodriquez ,&nbsp;Jamie Daniel ,&nbsp;Joshua Hayden","doi":"10.1016/j.jmsacl.2024.05.001","DOIUrl":"10.1016/j.jmsacl.2024.05.001","url":null,"abstract":"<div><p>Liquid handlers (LHs) have become common in both clinical and academic laboratories for the preparation and manipulation of samples. In theory, these systems offer the potential for reduced error due to the elimination of mis-pipetting errors. In reality, these systems still have potential for mis-pipetting and require careful validation by the end user. In this case report, we describe two instances where inappropriate pipetting by a vendor-programmed LH were observed. In each case, the worklist that was obtained from the LH failed to reflect what had actually been pipetted and as such these instances represented significant near misses with substantial potential for patient harm. Neither of these instances were caught during the laboratory’s validation studies of the LH. Laboratories should be aware of the potential for mis-pipetting by LHs. LH vendors should work to ensure the worklists reflect what was pipetted (instead of what was intended to be pipetted) and end users must ensure robust validation studies that take into account as many “real world” scenarios as possible.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"33 ","pages":"Pages 1-3"},"PeriodicalIF":2.2,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X24000208/pdfft?md5=13b219961c79039e46a2d0d6bcd1e1af&pid=1-s2.0-S2667145X24000208-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141043732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitation of propofol metabolites by LC–MS/MS demonstrating long detection window for urine drug monitoring","authors":"Thomas G. Rosano ,&nbsp;Michelle Wood ,&nbsp;Kiley L. Scholz ,&nbsp;Kiera Whitely ,&nbsp;Nathaniel Kim ,&nbsp;Melissa Ehlers","doi":"10.1016/j.jmsacl.2024.04.001","DOIUrl":"https://doi.org/10.1016/j.jmsacl.2024.04.001","url":null,"abstract":"<div><h3>Introduction</h3><p>Chromatographic methods for analysis of propofol and its metabolites have been widely used in pharmacokinetic studies of propofol distribution, metabolism, and clearance. Application of chromatographic methods is also needed in clinical and forensic laboratories for detecting and monitoring propofol misuse.</p></div><div><h3>Objective</h3><p>We report a method for sensitive analysis of propofol, propofol 1-glucuronide (PG), 4-hydroxypropofol 1-glucuronide (1-QG), 4-hydroxypropofol 4-glucuronide (4-QG) and 4-hydroxypropofol 4-sulfate (4-QS) in urine by LC–MS/MS analysis. The method employs a simple dilute-and-analyze sample preparation with stable isotope internal standardization.</p></div><div><h3>Results</h3><p>Validation studies demonstrate a linear calibration model (100–10,000 ng/mL), with dilution integrity verified for the extended range of concentrations experienced in propofol use. Criteria-based validation was achieved, including an average coefficient of variation of 6.5 % and a percent bias of −4.2 ng/mL. The method was evaluated in 12 surgical patients, with monitoring periods lasting up to 30 days following intravenous propofol administrations of 100–3000 mg on the day of surgery. While the concentration ratio of PG to 4-hydroxy propofol metabolite decreased significantly in the days following surgery, PG maintained the highest concentration in all specimens. Both PG and 1-QG were detectable throughout the monitoring periods, including in a patient monitored for 30 days. Lower concentrations were determined for 4-QG and 4-QS, with evidence of detection up to 20 days. Propofol was not detectable in any urine specimens, thereby proving ineffective for identifying drug use.</p></div><div><h3>Conclusion</h3><p>The validated method for quantifying propofol metabolites demonstrates its applicability for the sensitive detection of propofol misuse over a long window of drug-use detection.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"32 ","pages":"Pages 60-67"},"PeriodicalIF":2.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X24000191/pdfft?md5=18d77756ab2034ba58526495d0704b3b&pid=1-s2.0-S2667145X24000191-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140650027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of an LC-MSMS method to quantify creatinine from dried blood spots","authors":"Carlos Torres ,&nbsp;Rogers A. Muldrow ,&nbsp;Anissa R. Naranjo ,&nbsp;Steven W. Cotten ,&nbsp;Christina C. Pierre ,&nbsp;Dina N. Greene","doi":"10.1016/j.jmsacl.2024.03.001","DOIUrl":"10.1016/j.jmsacl.2024.03.001","url":null,"abstract":"<div><h3>Introduction</h3><p>Screening for chronic kidney disease relies on accurate and precise creatinine measurements. Traditionally, creatinine is measured in serum or plasma using high-throughput chemistry analyzers. However, dried blood spots (DBS) can also be utilized to improve testing access.</p></div><div><h3>Methods</h3><p>Samples were obtained from a 6 mm DBS punch, which was reconstituted in water before undergoing an acetonitrile crash. The resulting supernatant was diluted using an 80:20 acetonitrile: water before injection. Creatinine was identified using an isocratic gradient, and detected using an API 4000 triple quadrupole mass analyzer. Quantification relied on matrix-matched calibrators, with values harmonized to the Roche Cobas enzymatic assay. Validation studies assessing method performance included precision, linearity, accuracy, method comparison, stability, interference, and matrix effects.</p></div><div><h3>Results</h3><p>The LC-MSMS assay was linear from 0.3 to 20 mg/dL (y = 1.02x-0.11; R² = 0.996). Precision ranged from 5.2 to 8.1 % using matrix-matched controls (n = 4) that spanned the analytical measurement range. LC-MSMS results corresponded to the enzymatic assay (Roche) with a fitted line equation of y = 0.956x–0.07 (R² = 0.995; n = 173). The Siemens and Roche enzymatic assays demonstrated higher accuracy in correlating to the DBS creatinine concentration (n = 40 paired venous/DBS collections) compared to the Beckman Jaffe assay (-2.5 % and −0.8 % versus −6.3 % and −4.1 %, respectively) or the iSTAT (-28.4 % and −27.1 %, respectively). Accuracy was unaffected by hematocrit, blood spot volume, excess IgG or IgA, or hypertriglyceridemia. No matrix effects were observed, and both extraction and processing efficiency were robust.</p><p>Ambient stability extended to at least 10 days, and exposure to extreme temperature did not affect the creatinine results.</p></div><div><h3>Conclusion</h3><p>We successfully developed an accurate and precise LC-MSMS method for quantifying creatinine in DBS.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"32 ","pages":"Pages 50-59"},"PeriodicalIF":2.2,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X2400018X/pdfft?md5=638b4d1264304250726cb06f55f907de&pid=1-s2.0-S2667145X2400018X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140070230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pseudo-hypertriglyceridemia in a 2-year-old male with global developmental delay, myopathy and adrenal hypoplasia","authors":"Xiaowei Fu ,&nbsp;Claire P. Williamson ,&nbsp;Kerri Bosfield","doi":"10.1016/j.jmsacl.2024.02.004","DOIUrl":"https://doi.org/10.1016/j.jmsacl.2024.02.004","url":null,"abstract":"<div><p>Pseudo-hypertriglyceridemia is an overestimation of serum triglyceride levels due to laboratory assays that measure free glycerol concentrations instead of triglycerides directly. Consequently, conditions presenting with elevated levels of endogenous or exogenous free glycerol, such as glycerol kinase deficiency, result in an overestimation of serum triglycerides.<!--> <!-->Glycerol kinase deficiency (GKD) is caused by pathogenic variants of the <em>GK</em> gene on chromosome Xp21. GKD is characterized biochemically by hyperglycerolaemia and glyceroluria. We herein report a 2-year-old male presented with a history of global developmental delay, axial hypotonia, poor head control and inability to sit unassisted or walk with elevated triglycerides at 683 (normal 44-157 mg/dL). Organic acid analysis showed abnormal accumulation of glycerol. Chromosomal microarray results showed a 4.2 Mb deletion of Xp21.3p21.1 (29296579–33551038) including complete copies of <em>GK</em>, <em>DMD</em>, and <em>NR0B1</em> genes as well as multiple exons of <em>IL1RAPL1</em>. This confirmed his glycerol kinase deficiency (GKD) as part of the Xp21 continuous gene deletion syndrome. Elevated triglycerides were then recognized as pseudo-hypertriglyceridemia after the diagnosis. The younger sister and the mother have presented with developmental delay, and have been found to have same mutation.<!--> <!-->This family highlights the importance recognizing pseudohypertriglyceridemia and diagnostic challenges. Earlier identification through urine organic acid analysis could have been made. The combination of clinical presentations and increased glycerol should cause suspicion for GKD</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"32 ","pages":"Pages 47-49"},"PeriodicalIF":2.2,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X24000178/pdfft?md5=00627178e47439b481915d6241eb977a&pid=1-s2.0-S2667145X24000178-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139936792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous monoclonal immunoglobulins analyzed using the EXENT® solution and LC-MS","authors":"David Barnidge ,&nbsp;Derek Troske ,&nbsp;Simon North ,&nbsp;Gregg Wallis ,&nbsp;Mark Perkins ,&nbsp;Stephen Harding","doi":"10.1016/j.jmsacl.2024.02.002","DOIUrl":"https://doi.org/10.1016/j.jmsacl.2024.02.002","url":null,"abstract":"<div><h3>Introduction</h3><p>The EXENT® Solution, a fully automated system, is a recent advancement for identifying and quantifying monoclonal immunoglobulins in serum. It combines immunoprecipitation with MALDI-TOF mass spectrometry. Compared to gel-based methods, like SPEP and IFE, it has demonstrated the ability to detect monoclonal immunoglobulins in serum at lower levels. In this study, samples that tested negative using EXENT® were reflexed to LC-MS to determine if the more sensitive LC-MS method could identify monoclonal immunoglobulins missed by EXENT®.</p></div><div><h3>Objectives</h3><p>To assess whether monoclonal immunoglobulins that are not detected by EXENT® can be detected by LC-MS using a low flow LC system coupled to a Q-TOF mass spectrometer.</p></div><div><h3>Methods</h3><p>Samples obtained from patients confirmed to have multiple myeloma (MM) were diluted with pooled polyclonal human serum and analyzed using EXENT®. If a specific monoclonal immunoglobulin was not detected by EXENT®, the sample was then subjected to analysis by LC-MS. For the LC-MS analysis, the sample eluate, obtained after the MALDI-TOF MS spotting step, was collected and transferred to an autosampler tray for subsequent analysis using LC-MS.</p></div><div><h3>Conclusion</h3><p>LC-MS has the capability to detect monoclonal immunoglobulins that are no longer detected by EXENT®. Reflexing samples to LC-MS for analysis does not involve additional sample handling, allowing for a faster time-to-result compared to current approaches, such as Next-Generation Sequencing, Next-Generation Flow, and clonotypic peptide methods. Notably, LC-MS offers equivalent sensitivity in detecting these specific monoclonal immunoglobulins.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"32 ","pages":"Pages 31-40"},"PeriodicalIF":2.2,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X24000154/pdfft?md5=f1ce04da5778089272707013515f00cc&pid=1-s2.0-S2667145X24000154-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139907743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic drug monitoring of clozapine in human serum by high-throughput paper spray mass spectrometry","authors":"A. Saatchi ,&nbsp;T.M. Zarkovic ,&nbsp;S.A. Borden ,&nbsp;J. Palaty ,&nbsp;C.G. Gill","doi":"10.1016/j.jmsacl.2024.02.003","DOIUrl":"10.1016/j.jmsacl.2024.02.003","url":null,"abstract":"<div><h3>Introduction</h3><p>Monitoring the atypical antipsychotic drug clozapine is crucial to ensure patient safety. This article showcases a high-throughput analytical method for measuring clozapine and its primary metabolite norclozapine (N-desmethylclozapine) in serum using paper spray mass spectrometry (PS-MS).</p></div><div><h3>Objectives</h3><p>This study aimed to assess the viability of a PS-MS method for the rapid measurement of clozapine and norclozapine in human serum samples as an alternative to liquid chromatography mass spectrometry (LC-MS).</p></div><div><h3>Methods</h3><p>Serum samples were processed by protein precipitation followed by deposition of the supernatant containing labelled internal standards onto paper spray substrates mounted in cartridges. Analytes were then analyzed using a triple quadrupole mass spectrometer equipped with a commercial paper spray ionization source. The results obtained from the patient samples were compared to those from a validated LC-MS assay.</p></div><div><h3>Results</h3><p>PS-MS calibrations for clozapine and norclozapine were linear (R² &gt; 0.99) over five days. Between-run precision was below 8 %, and within-run precision did not exceed 10 %. When compared to a validated LC-MS method, the mean bias for 39 patient samples was −9% for clozapine and −1% for norclozapine, with no outliers. Mass spectrometry ion ratio comparisons indicated no interference for patient samples above the lower limit of quantification. There was less than 7 % change in the measured concentrations of both analytes over five days for samples dried on paper substrates. Notably, virtually no maintenance of the MS source was required during this study.</p></div><div><h3>Conclusion</h3><p>This study illustrates the potential of PS-MS for serum drug monitoring in the clinical laboratory.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"32 ","pages":"Pages 41-46"},"PeriodicalIF":2.2,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X24000166/pdfft?md5=801455da959bf187a1238dd67f5e64b1&pid=1-s2.0-S2667145X24000166-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139886849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}