Matthew A. Koc , Timothy Aaron Wiles , Daniel C. Weinhold, Steven Rightmyer, Amanda L. Weaver, Colin T. McDowell, Joanna Roder, Senait Asmellash, Gary A. Pestano, Heinrich Roder, Robert W. Georgantas III
{"title":"Molecular and translational biology of the blood-based VeriStrat® proteomic test used in cancer immunotherapy treatment guidance","authors":"Matthew A. Koc , Timothy Aaron Wiles , Daniel C. Weinhold, Steven Rightmyer, Amanda L. Weaver, Colin T. McDowell, Joanna Roder, Senait Asmellash, Gary A. Pestano, Heinrich Roder, Robert W. Georgantas III","doi":"10.1016/j.jmsacl.2023.11.001","DOIUrl":"https://doi.org/10.1016/j.jmsacl.2023.11.001","url":null,"abstract":"<div><h3>Introduction</h3><p>The VeriStrat® test (VS) is a blood-based assay that predicts a patient's response to therapy by analyzing eight features in a spectrum obtained from matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analysis of human serum and plasma. In a recent analysis of the INSIGHT clinical trial (NCT03289780), it was found that the VS labels, VS Good and VS Poor, can effectively predict the responsiveness of non-small cell lung cancer (NSCLC) patients to immune checkpoint inhibitor (ICI) therapy. However, while VS measures the intensities of spectral features using MALDI-TOF analysis, the specific proteoforms underlying these features have not been comprehensively identified.</p></div><div><h3>Objectives</h3><p>The objective of this study was to identify the proteoforms that are measured by VS.</p></div><div><h3>Methods</h3><p>To resolve the features obtained from the low-resolution MALDI-TOF procedure used to acquire mass spectra for VS DeepMALDI® analysis of serum was employed. This technique allowed for the identification of finer peaks within these features. Additionally, a combination of reversed-phase fractionation and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was then used to identify the proteoforms associated with these peaks.</p></div><div><h3>Results</h3><p>The analysis revealed that the primary constituents of the spectrum measured by VS are serum amyloid A1, serum amyloid A2, serum amyloid A4, C-reactive protein, and beta-2 microglobulin.</p></div><div><h3>Conclusion</h3><p>Proteoforms involved in host immunity were identified as significant components of these features. This newly acquired information improves our understanding of how VS can accurately predict patient response to therapy. It opens up additional studies that can expand our understanding even further.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"30 ","pages":"Pages 51-60"},"PeriodicalIF":2.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X23000354/pdfft?md5=43d2c758d2d2862f33f425c51e08b521&pid=1-s2.0-S2667145X23000354-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138328444","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}
Jessica M. Colón Franco , Rogers A. Muldrow , Wendy Cieslak , Patrick DeArmond , Cody Orahoske , Drew Payto , Dina N. Greene , Dustin Bunch
{"title":"Matrix-matched calibrators are necessary for robust and high-quality dried blood spots lead screening assays by inductively coupled plasma-mass spectrometry","authors":"Jessica M. Colón Franco , Rogers A. Muldrow , Wendy Cieslak , Patrick DeArmond , Cody Orahoske , Drew Payto , Dina N. Greene , Dustin Bunch","doi":"10.1016/j.jmsacl.2023.10.002","DOIUrl":"https://doi.org/10.1016/j.jmsacl.2023.10.002","url":null,"abstract":"<div><h3>Background and aims</h3><p>Reliable lead screening methods are necessary to support early identification of lead exposure in children. Sample collection using dried blood spots (DBS) offers advantages compared to traditional venipuncture and capillary collection. Here, we describe and compare three lead DBS inductively coupled plasma-mass spectrometry (ICP-MS) methods for lead screening.</p></div><div><h3>Materials and methods</h3><p>Lead was extracted from Whatman 903 protein saver cards punches and analyzed by ICP-MS across three independent clinical laboratories. Each laboratory evaluated the performance of aqueous and matrix-matched DBS calibrators using external quality control samples (WI State of Laboratory of Hygiene Program). Leftover patient samples (n = 39) were used for an interlaboratory comparison of lead DBS. Lead DBS results were compared to whole blood methods.</p></div><div><h3>Results</h3><p>The DBS ICP-MS methods using matrix-matched DBS calibrators had superior performance to the aqueous calibrations. There was a strong correlation between lead measured in DBS (matrix-matched) and whole blood for the three methods evaluated.</p></div><div><h3>Conclusion</h3><p>Lead can be measured accurately by ICP-MS in DBS samples when matrix-matched calibrators are used. External quality control programs are valuable to assess the performance of DBS methods. DBS lead ICP-MS methods are a robust analytical option for lead screening even though the limitations of DBS are well recognized.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"30 ","pages":"Pages 45-50"},"PeriodicalIF":2.2,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667145X23000342/pdfft?md5=25677bae580c0f61d25cd4a108b2f2c4&pid=1-s2.0-S2667145X23000342-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91594491","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":"Improving LC-MS/MS measurements of steroids with differential mobility spectrometry","authors":"Yubo Chai , Stefan K.G. Grebe , Anthony Maus","doi":"10.1016/j.jmsacl.2023.10.001","DOIUrl":"10.1016/j.jmsacl.2023.10.001","url":null,"abstract":"<div><h3>Introduction</h3><p>Steroid measurements are important for diagnosis and monitoring of many conditions and treatment regiments; however, due to structural and chemical similarities amongst steroids, these analyses are challenging, even for highly specific techniques such as liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differential mobility spectrometry (DMS) has the potential to improve these analyses by providing an orthogonal and complementary separation technique.</p></div><div><h3>Methods</h3><p>Initially, the potential for DMS to improve signal-to-noise ratio (S/N) and reduce interference was tested by comparing chromatograms acquired with and without DMS when performing measurements of six different steroids. Subsequently, a full clinical validation of cortisol and cortisone in urine was performed with the LC-DMS-MS/MS method.</p></div><div><h3>Results and Discussion</h3><p>DMS significantly reduced interferences observed in the chromatograms and boosted S/N by between 1.6 and 13.8 times. Additionally, DMS improved the agreement between quantifier/qualifier fragment ion results for cortisol and cortisone as indicated by the increase in R<sup>2</sup> from approximately 0.81 to 0.98. All validation studies met acceptance criteria and we observed exceptional analytical performance in terms of precision, with % CVs less than 8%.</p></div><div><h3>Conclusions</h3><p>DMS improved the specificity of the steroid measurements by reducing interferences and improving S/N. The validation studies prove that these benefits did not come at the expense of other aspects of analytical performance. This study indicates that DMS has the potential to benefit not just clinical measurements of challenging analytes, but many clinical LC-MS/MS analyses.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"30 ","pages":"Pages 30-37"},"PeriodicalIF":2.2,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1b/f8/main.PMC10582739.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49684914","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}
Xue Li Guan , Dorothy Pei Shan Chang , Zhen Xuan Mok , Bernett Lee
{"title":"Assessing variations in manual pipetting: An under-investigated requirement of good laboratory practice","authors":"Xue Li Guan , Dorothy Pei Shan Chang , Zhen Xuan Mok , Bernett Lee","doi":"10.1016/j.jmsacl.2023.09.001","DOIUrl":"10.1016/j.jmsacl.2023.09.001","url":null,"abstract":"<div><p>Pipettes are essential tools for biomedical and analytical laboratories, analogous to workstations for computer scientists. Variation in pipetting is a known unknown, as it is generally accepted that variations exist, but thus far, there have been limited studies on the extent of these variations in practice. In this mini-review, we highlight how manual pipetting is a key technique in the laboratory, and, although simple, inaccuracy and imprecision exist. If variations are not adequately addressed, errors can be compounded and consequently compromise data quality. Determination of the accuracy and precision of manual pipetting is straightforward, and here we review two common approaches that use gravimetry and spectrophotometry as readouts. We also provide detailed protocols for determination of accuracy and precision using manual single and multi-channel pipettes. These simple-to-use methods can be used by any laboratory for competency training and regular checks. Having a common protocol for evaluation of variation will also enable cross-laboratory comparison and potentially facilitate establishment of a reference value of acceptable ranges for operator error. Such a value could be of relevance to the scientific community for benchmarking and assuring good laboratory practice.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"30 ","pages":"Pages 25-29"},"PeriodicalIF":2.2,"publicationDate":"2023-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/45/bd/main.PMC10569977.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41240812","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}
Ruben Yiqi Luo , Kate Comstock , Caroline Ding , Alan H.B. Wu , Kara L. Lynch
{"title":"Comparison of liquid chromatography-high-resolution tandem mass spectrometry (MS2) and multi-stage mass spectrometry (MS3) for screening toxic natural products","authors":"Ruben Yiqi Luo , Kate Comstock , Caroline Ding , Alan H.B. Wu , Kara L. Lynch","doi":"10.1016/j.jmsacl.2023.09.002","DOIUrl":"https://doi.org/10.1016/j.jmsacl.2023.09.002","url":null,"abstract":"<div><h3>Background</h3><p>Liquid chromatography-high-resolution mass spectrometry (LC-HR-MS) has emerged as a powerful analytical technology for compound screening in clinical toxicology. To evaluate the potential of LC-HR-MS<sup>3</sup> in detecting toxic natural products, a spectral library of 85 natural products (79 alkaloids) that contains both MS<sup>2</sup> and MS<sup>3</sup> mass spectra was constructed and used to identify the natural products. Samples were analyzed using an LC-HR-MS<sup>3</sup> method and the generated data were matched to the spectral library to identify the natural products.</p></div><div><h3>Methods</h3><p>To test the performance of the LC-HR-MS<sup>3</sup> method in different sample matrices, the 85 natural product standards were divided into three groups to separate structural isomers and avoid ion suppression effects caused by co-elution of multiple analytes. The grouped analytes were spiked into drug-free serum and drug-free urine to produce contrived clinical samples.</p></div><div><h3>Results</h3><p>The compound identification results of the 85 natural products in urine and serum samples were obtained. The match scores using both MS<sup>2</sup> and MS<sup>3</sup> mass spectra and those using only MS<sup>2</sup> mass spectra were compared at 10 different analyte concentrations. The two types of data analysis provided identical identification results for the majority of the analytes (96% in serum, 92% in urine), whereas, for the remaining analytes, the MS<sup>2</sup>-MS<sup>3</sup> tree data analysis had better performance in identifying them at lower concentrations.</p></div><div><h3>Conclusion</h3><p>This study shows that in comparison to LC-HR-MS (MS<sup>2</sup>), LC-HR-MS<sup>3</sup> can increase the performance in identification of a small group of the toxic natural products tested in serum and urine specimens.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"30 ","pages":"Pages 38-44"},"PeriodicalIF":2.2,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49763440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"GC–MS and GC–MS/MS measurement of malondialdehyde (MDA) in clinical studies: Pre-analytical and clinical considerations","authors":"Dimitrios Tsikas","doi":"10.1016/j.jmsacl.2023.08.001","DOIUrl":"10.1016/j.jmsacl.2023.08.001","url":null,"abstract":"<div><p>Malondialdehyde (MDA; 1,3-propanedial, OHC-CH<sub>2</sub>-CHO) is one of the most frequently measured biomarkers of oxidative stress in plasma and serum. L-Arginine (Arg) is the substrate of nitric oxide synthases (NOS), which convert L-arginine to nitric oxide (NO) and L-citrulline. The Arg/NO pathway comprises several members, including the endogenous NOS-activity inhibitor asymmetric dimethylarginine (ADMA) and its major metabolite dimethyl amine (DMA), and nitrite and nitrate, the major NO metabolites. Reliable measurement of MDA and members of the Arg/NO pathway in plasma, serum, urine and in other biological samples, such as saliva and cerebrospinal fluid, is highly challenging both for analytical and pre-analytical reasons. In our group, we use validated gas chromatography-mass spectrometry (GC–MS) and gas chromatography-tandem mass spectrometry (GC–MS/MS) methods for the quantitative determination in clinical studies of MDA as a biomarker of oxidative stress, and various Arg/NO metabolites that describe the status of this pathway. Here, the importance of pre-analytical issues, which has emerged from the use of GC–MS and GC–MS/MS in clinico-pharmacological studies, is discussed. Paradigmatically, two studies on the long-term oral administration of L-arginine dihydrochloride to patients suffering from peripheral arterial occlusive disease (PAOD) or coronary artery disease (CAD) were considered. Pre-analytical issues that were addressed include blood sampling, plasma or serum storage, study design (notably in long-term studies), and the alternative of measuring MDA in human urine.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"30 ","pages":"Pages 10-24"},"PeriodicalIF":2.2,"publicationDate":"2023-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b2/6c/main.PMC10458701.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10112178","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}
Sina Junger , Miriam Hoene , Maria Shipkova , Gudrun Danzl , Christof Schöberl , Andreas Peter , Rainer Lehmann , Eberhard Wieland , Helmine Braitmaier
{"title":"Automated LC-MS/MS: Ready for the clinical routine Laboratory?","authors":"Sina Junger , Miriam Hoene , Maria Shipkova , Gudrun Danzl , Christof Schöberl , Andreas Peter , Rainer Lehmann , Eberhard Wieland , Helmine Braitmaier","doi":"10.1016/j.jmsacl.2023.07.001","DOIUrl":"10.1016/j.jmsacl.2023.07.001","url":null,"abstract":"<div><h3>Background</h3><p>Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a sensitive method with high specificity. However, its routine use in the clinical laboratory is hampered by its high complexity and lack of automation. Studies demonstrate excellent analytical performance using the first fully automated LC-MS/MS for 25-hydroxy vitamin D and immunosuppressant drugs (ISD) in hospital routine laboratories.</p></div><div><h3>Objectives</h3><p>Our objectives were (1) to verify the suitability of an automated LC-MS/MS in a commercial laboratory, which differs from the needs of hospital laboratories, and (2) examine its usability among operators with various professional backgrounds.</p></div><div><h3>Methods</h3><p>We assessed the analytical assay performance for vitamin D and the ISDs cyclosporine A and tacrolimus over five months. The assays were compared to an identical analyzer in a hospital laboratory, to in-house LC-MS/MS methods, and to chemiluminescent microparticle immunoassays (CMIA). Nine operators evaluated the usability of the fully automated LC-MS/MS system by means of a structured questionnaire.</p></div><div><h3>Results</h3><p>The automated system exhibited a high precision (CV < 8%), accuracy (bias < 7%) and good agreement with concentrations of external quality assessment (EQA) samples. Comparable results were obtained with an identical analyzer in a hospital routine laboratory. Acceptable median deviations of results versus an in-house LC-MS/MS were observed for 25-OH vitamin D3 (-10.6%), cyclosporine A (-4.3%) and tacrolimus (-6.6%). The median bias between the automated system and immunoassays was only acceptable for 25-OH vitamin D3 (6.6%). All users stated that they had had a good experience with the fully automated LC-MS/MS system.</p></div><div><h3>Conclusions</h3><p>A fully automated LC-MS/MS can be easily integrated for routine diagnostics in a commercial laboratory.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"30 ","pages":"Pages 1-9"},"PeriodicalIF":2.2,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ab/cb/main.PMC10423925.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10366892","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 clinical application of a liquid chromatography-tandem mass spectrometry-based assay to quantify eight tyrosine kinase inhibitors in human plasma","authors":"Fangjun Chen , Wenda Chen , Zhenxin Wang , Yingfei Peng, Beili Wang, Baishen Pan, Wei Guo","doi":"10.1016/j.jmsacl.2023.05.001","DOIUrl":"10.1016/j.jmsacl.2023.05.001","url":null,"abstract":"<div><h3>Introduction</h3><p>Tyrosine kinase inhibitors (TKIs) are widely used in tumor treatment. The detection of these medicines by liquid chromatography-tandem mass spectrometry (LC-MS/MS) can avoid the interference of structurally similar compounds.</p></div><div><h3>Objectives</h3><p>This study aimed to develop and validate a new LC-MS/MS assay for the quantification of eight tyrosine kinase inhibitors in human plasma and to preliminarily evaluate the clinical utility of the therapeutic drug monitoring method.</p></div><div><h3>Methods</h3><p>Plasma samples were prepared by simple protein precipitation and separated using an ultra-high-performance reversed phase column. Detection was achieved using a triple quadrupole mass spectrometer in the positive ionization mode. The assay was validated against standard guidelines. We reviewed and analyzed the results of 268 plasma samples obtained from patients administered imatinib and other TKIs collected from January 2020 to November 2021 at Zhongshan Hospital. The analytes were separated and quantified within 3.5 min.</p></div><div><h3>Results</h3><p>The newly developed method demonstrated linearity for the detected drug concentration in the range of 20 to 2000 ng/ml for gefitinib (r<sup>2</sup> = 0.991) and crizotinib (r<sup>2</sup> = 0.992), 50 to 5000 ng/ml for nilotinib (r<sup>2</sup> = 0.991) and imatinib (r<sup>2</sup> = 0.995), 1500–150,000 ng/ml for vemurafenib (r<sup>2</sup> = 0.998), 1000–100,000 ng/ml for pazopanib (r<sup>2</sup> = 0.993), 0.5–100 ng/ml for axitinib (r<sup>2</sup> = 0.992) and 5–500 ng/ml for sunitinib (r<sup>2</sup> = 0.991) and N-desethyl sunitinib (r<sup>2</sup> = 0.998). The lower limit of quantification (LLOQ) was 20 ng/ml for gefitinib and crizotinib, 50 ng/ml for nilotinib and imatinib, 1500 ng/ml for vemurafenib, 1000 ng/ml for pazopanib, 0.5, and 5 ng/ml for sunitinib and N-desethyl sunitinib, respectively. Specificity, precision, accuracy, and stability were tested, and met the requirements of the guidelines. At the same dose, there was no significant difference in plasma drug concentration between the original imatinib medicine and the generic medicine after patent expiration.</p></div><div><h3>Conclusion</h3><p>We developed a sensitive and reliable method for the quantification of eight TKIs.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"29 ","pages":"Pages 2-8"},"PeriodicalIF":2.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dd/e4/main.PMC10205537.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9881089","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}
Melissa M Budelier, Mark A Marzinke, Jacqueline A Hubbard
{"title":"An introduction from the Laboratory Developed Tests special issue guest editors","authors":"Melissa M Budelier, Mark A Marzinke, Jacqueline A Hubbard","doi":"10.1016/j.jmsacl.2023.05.002","DOIUrl":"https://doi.org/10.1016/j.jmsacl.2023.05.002","url":null,"abstract":"","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"29 ","pages":"Page 1"},"PeriodicalIF":2.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49741934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew L. Crawford, Christopher M. Shuford, Russell P. Grant
{"title":"The pipetting Olympics: Propagating proper pipetting a priori in clinical LC-MS/MS analysis","authors":"Matthew L. Crawford, Christopher M. Shuford, Russell P. Grant","doi":"10.1016/j.jmsacl.2023.06.002","DOIUrl":"https://doi.org/10.1016/j.jmsacl.2023.06.002","url":null,"abstract":"<div><h3>Introduction</h3><p>Engaging pipetting events were developed to assess and challenge technicians’ practical sample handling using matrices common to the clinical laboratory. As correct pipetting stands as a prerequisite for accurate clinical laboratory testing, this helped to understand sources of imprecision and bias attributed to the underlying step of aspirating and dispensing patient samples and internal standard in clinical LC-MS/MS assays while highlighting the importance for the clinical laboratory to evaluate this source of variability on an on-going basis and mitigate its impact.</p></div><div><h3>Methods</h3><p>The events involved pipetting water, methanol, serum, and whole blood. Gravimetric analysis was used to determine the exact volumetric delivery of each matrix using two different techniques. Imprecision and bias were calculated based on the volume derived from the mass and density of each matrix, using literature values for each matrix type.</p></div><div><h3>Results</h3><p>Low imprecision and bias were observed when pipetting water, as in common commercial pipetting assessment programs. Significantly increased imprecision and bias were observed in more applicable matrices (i.e., serum, whole blood, and methanol), indicating that water-based pipetting proficiency assessment leads to a false sense of technical ability. Additionally, the events within illuminated areas for training, leading to improved imprecision and bias. It was shown that pre-rinsing (aspirating and dispensing matrix three times to coat the tip) improved bias, particularly for delivery of methanol and whole blood.</p></div><div><h3>Conclusions</h3><p>Precise and accurate pipetting within the clinical laboratory should not be taken for granted, nor implicitly inferred from proficiency assessment using aqueous solutions. The engaging and collegial events fostered training opportunities. Assay-specific patient sample delivery considerations (pipets and matrices) can inform the practicality of these events – the Pipetting Olympics – and drive improvements within the laboratory.</p></div>","PeriodicalId":52406,"journal":{"name":"Journal of Mass Spectrometry and Advances in the Clinical Lab","volume":"29 ","pages":"Pages 16-20"},"PeriodicalIF":2.2,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49741704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}