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

{"title":"Rapid identification of SARS CoV-2 omicron sub-variant JN.1 (BA.2.86.1.1) with mass spectrometry","authors":"Henry E. Lanyon,&nbsp;Kevin M. Downard","doi":"10.1016/j.jmsacl.2024.08.003","DOIUrl":"10.1016/j.jmsacl.2024.08.003","url":null,"abstract":"<div><h3>Objective</h3><p>The rapid detection and differentiation of strains of the BA.2.86 lineage including the new sub-variant JN.1 (BA.2.86.1.1) is demonstrated employing selected ion monitoring (SIM) and high resolution mass spectrometry.</p></div><div><h3>Methods</h3><p>A study of a preliminary set of BA.2.86 lineage positive specimens, identified BA.2.86 and BA.2.86.1.1 peptide markers in 62.5 % and 29.1 % of samples.</p></div><div><h3>Results</h3><p>Peptide-specific markers in the surface spike protein associated with the L455S mutation are confidently detected with high sensitivity in protein and virus digests.</p><p>The virus was thus confidently assigned in over 91 % of positive specimens.</p></div><div><h3>Conclusions</h3><p>A rise in the global prevalence of the JN.1 (BA.2.86.1.1) immune evasive sub-variant, that emerged in late 2023, requires that new strategies and protocols to detect such strains in human specimens are accelerated and implemented.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"33 ","pages":"Pages 38-42"},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X24000294/pdfft?md5=1ccf05ce3d97520e6ac37ad4c6ea2d3e&pid=1-s2.0-S2667145X24000294-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049716","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":"Isotope-dilution-LC-MS/MS candidate reference measurement procedure for cefepime in human serum","authors":"Judith Schäffler,&nbsp;Michael Vogeser,&nbsp;Katharina Habler","doi":"10.1016/j.jmsacl.2024.08.001","DOIUrl":"10.1016/j.jmsacl.2024.08.001","url":null,"abstract":"<div><h3>Background</h3><p>Reference measurement procedures are an essential element in the standardization and comparability of analytical measurement results in laboratory medicine. No LC-MS/MS-based reference measurement procedure for cefepime in serum has been published previously.</p></div><div><h3>Materials and methods</h3><p>An isotope-dilution based two-dimensional LC-MS/MS reference measurement procedure for cefepime concentrations in human serum was developed and tested. The value assignment of unknown samples is based on a defined measurement series validation. Six unknown samples can be measured per series. Pass criteria for the run and the samples were determined empirically based on a performance evaluation. For this purpose, a between-run determination of five runs of the defined measurement series with six cefepime samples was carried out and evaluated. The goal was to define rigorous, realistic target limits and minimize measurement uncertainty. The final defined target limits are used for series-based validation and value assignment. The results for the six unknown samples are provided with the associated measurement uncertainty for this series.</p></div><div><h3>Results</h3><p>The developed and extensively studied measurement procedure for the quantification of cefepime in serum was found to be practicable and fit for its purpose. The between-run mean imprecision of the six cefepime samples was ≤ 2.0 %, for the QCs it was ≤ 2.3 % and the between-run mean inaccuracy of the QCs was within ± 1.1 %.</p></div><div><h3>Conclusion</h3><p>The novel isotope-dilution-LC-MS/MS measurement procedure in accordance to ISO 15193 can be recommended as candidate reference measurement procedure for the value assignment of cefepime concentrations in human serum.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"33 ","pages":"Pages 43-48"},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X24000270/pdfft?md5=c3632916c031e097ca0bd9757cab300c&pid=1-s2.0-S2667145X24000270-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142058451","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":"Impact of internal standard selection on measurement results for long chain fatty acids in blood","authors":"John M. Goodwin VII,&nbsp;Heather C. Kuiper,&nbsp;Barrett Brister,&nbsp;Hubert W. Vesper","doi":"10.1016/j.jmsacl.2024.07.002","DOIUrl":"10.1016/j.jmsacl.2024.07.002","url":null,"abstract":"<div><h3>Introduction</h3><p>Internal standards correct for measurement variation due to sample loss. Isotope labeled analytes are ideal internal standards for the measurement of fatty acids in human plasma but are not always readily available. For this reason, quantification of multiple analytes at once is most often done using only a single or few internal standards. The magnitude of the impact this has on method accuracy and precision is not well studied for gas chromatography-mass spectrometry systems.</p></div><div><h3>Objective</h3><p>This study aims to estimate bias and changes in uncertainty associated with using alternative fatty acid isotopologue internal standards for the estimation of similar or dissimilar long chain fatty acids.</p></div><div><h3>Method</h3><p>Using a previously reported method for the quantification of 27 fatty acids in human plasma using 18 internal standards we obtained estimates of bias and uncertainty at up to three levels of fatty acid concentration.</p></div><div><h3>Results</h3><p>With some notable exceptions, method accuracy remained relatively stable when using an alternative internal standard (Median Relative Absolute Percent Bias: 1.76%, Median Spike-Recovery Absolute Percent Bias: 8.82%), with larger changes in method precision (Median Increase in Variance: 141%). Additionally, the degree of difference between analyte and internal standard structure was related to the magnitude of bias and uncertainty of the measurement.</p></div><div><h3>Conclusion</h3><p>The data presented here show that the choice of internal standard used to estimate fatty acid concentration can affect the accuracy and reliability of measurement results and, therefore, needs to be assessed carefully when developing analytical methods for the measurement of fatty acid profiles.</p><p>Disclaimer: The findings and conclusions in this report are those of the author(s) and do not necessarily represent the official position of the Centers for Disease Control and Prevention/the Agency for Toxic Substances and Disease Registry. Use of trade names is for identification only and does not imply endorsement by the Centers for Disease Control and Prevention, the Public Health Service, and the US Department of Health and Human Services.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"33 ","pages":"Pages 22-30"},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X24000257/pdfft?md5=5b14caa1db281421162ac06d9d0ebfcc&pid=1-s2.0-S2667145X24000257-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141930897","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":"Comparison between a single- and a multi-point calibration method using LC-MS/MS for measurement of 5-fluorouracil in human plasma","authors":"Mirjana Radovanovic ,&nbsp;Jennifer J. Schneider ,&nbsp;Jennifer H. Martin ,&nbsp;Ross L.G. Norris ,&nbsp;Peter Galettis","doi":"10.1016/j.jmsacl.2024.07.003","DOIUrl":"10.1016/j.jmsacl.2024.07.003","url":null,"abstract":"<div><p>When quantifying therapeutic drugs using LC-MS/MS instrumentation in clinical laboratories, batch-mode analysis with a calibration curve consisting of 6–10 concentrations for each analyte is the most widely used approach. However, this is an inefficient use of this technology since it increases cost, delays result availability and precludes random instrument access. Various alternative methods to reduce the calibrator use and improve efficiency without compromising analytical quality have been investigated, and a single-point calibration has been reported to be the simplest, least expensive and the quickest approach.</p><p>This study compares a single and a multi-point calibration method using LC-MS/MS with 5-fluorouracil (5-FU) as a model drug. The method was validated for quantitative analysis of 5-FU over a concentration range of 0.05–50 mg/L. Patients undergoing cancer treatment with intravenous 5-FU had plasma 5-FU concentrations measured, and their dose adjusted in real time based on the calculated area under the time-concentration curve (AUC). Subsequently, a single point calibration method using a concentration at 0.5 mg/L was compared to the multi-point calibration method in terms of accuracy and precision. A Bland-Altman bias plot and a Passing-Bablok regression analysis showed a good agreement between the two methods (mean difference = −1.87 %, slope = 1.002, respectively) when comparing patient plasma 5-FU concentrations. The calibration method did not impact the AUC results nor the decision on 5-FU dose adjustments. Our study demonstrated that a single point calibration method produced analytically and clinically comparable results to those produced by a multi-point method when quantifying 5-FU and is feasible to be used clinically.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"33 ","pages":"Pages 31-37"},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X24000269/pdfft?md5=71c8aefa7eebe9f1f1595131d3b2cfec&pid=1-s2.0-S2667145X24000269-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141930898","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":"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 ,&nbsp;Rebecca D. Ganetzky ,&nbsp;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}