Development and Validation of Small Molecule Analytes by Liquid Chromatography-Tandem Mass Spectrometry

Grant, Russell P.; Rappold, Brian A.

doi:10.1016/b978-0-12-816063-3.00005-0

Cited by 11 publications

(13 citation statements)

References 38 publications

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“…Some studies have indicated that this determination can be made solely on theoretical grounds [ 54 , 55 ]. However, empirical determination, which experimentally defines the optimal solvent characteristics for maximal response, has been suggested [ 56 ]. Briefly, a single concentration of an analyte is fortified into various solvent mixtures comprised of possible weak and strong solvents.…”

Section: Chromatography Developmentmentioning

confidence: 99%

“…Chromatographic screening utilizing solvents as determined in an ionization efficiency screening has been discussed elsewhere [ 56 , 63 ]. The process of chromatographic screening can be informed by important metrics, such as absolute abundance, retention time, cycle time, peak width, noise/baseline height, and relative retention time/resolution.…”

Section: Chromatography Developmentmentioning

confidence: 99%

“…Novel pipetting systems have been developed to support formats typical for liquid handling footprints [ 77 , 78 ]. In either liquid or supported form, conditions should be optimized for the compound(s) of interest [ 56 ]. This can include testing individual solvents as well as solvent mixtures to achieve the most appropriate extract [ 79 ].…”

Section: Sample Extractionmentioning

confidence: 99%

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Review of the Use of Liquid Chromatography-Tandem Mass Spectrometry in Clinical Laboratories: Part I-Development

Rappold

2022

Ann Lab Med

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The process of method development for a diagnostic assay based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) involves several disparate technologies and specialties. Additionally, method development details are typically not disclosed in journal publications. Method developers may need to search widely for pertinent information on their assay(s). This review summarizes the current practices and procedures in method development. Additionally, it probes aspects of method development that are generally not discussed, such as how exactly to calibrate an assay or where to place quality controls, using examples from the literature. This review intends to provide a comprehensive resource and induce critical thinking around the experiments for and execution of developing a clinically meaningful LC-MS/MS assay.

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Section: Chromatography Developmentmentioning

confidence: 99%

Section: Chromatography Developmentmentioning

confidence: 99%

Section: Sample Extractionmentioning

confidence: 99%

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Review of the Use of Liquid Chromatography-Tandem Mass Spectrometry in Clinical Laboratories: Part I-Development

Rappold

2022

Ann Lab Med

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“…An entire chapter of the Tietz Textbook of Clinical Chemistry is dedicated to a distillation of the FDA BMV, CLSI guidelines, and general best practices for the execution of LC-MS/MS validation [ 8 ]. It prescribes batch sizes, replicates, designs, and timeframes for validation experiments.…”

Section: Validationmentioning

confidence: 99%

“…Perhaps the most critical materials in LC-MS/MS assays are calibration standards used to generate a calibration curve. On a practical level, the entire LC-MS/MS procedure has no intrinsic accuracy requirement, but rather, within-batch precision is the goal [ 8 ]. For example, an imaginary assay SOP states that “50 µL of sample, calibrator, QC, or blank shall be aliquoted to each well of a 96-well plate.” If a technician inadvertently aliquots 55 µL for each of the sample types, this will not result in a 10% bias in the data.…”

Section: Assay Maintenancementioning

confidence: 99%

Review of the Use of Liquid Chromatography-Tandem Mass Spectrometry in Clinical Laboratories: Part II–Operations

Rappold

2022

Ann Lab Med

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Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is increasingly utilized in clinical laboratories because it has advantages in terms of specificity and sensitivity over other analytical technologies. These advantages come with additional responsibilities and challenges given that many assays and platforms are not provided to laboratories as a single kit or device. The skills, staff, and assays used in LC-MS/MS are internally developed by the laboratory, with relatively few exceptions. Hence, a laboratory that deploys LC-MS/MS assays must be conscientious of the practices and procedures adopted to overcome the challenges associated with the technology. This review discusses the post-development landscape of LC-MS/MS assays, including validation, quality assurance, operations, and troubleshooting. The content knowledge of LC-MS/MS users is quite broad and deep and spans multiple scientific fields, including biology, clinical chemistry, chromatography, engineering, and MS. However, there are no formal academic programs or specific literature to train laboratory staff on the fundamentals of LC-MS/MS beyond the reports on method development. Therefore, depending on their experience level, some readers may be familiar with aspects of the laboratory practices described herein, while others may be not. This review endeavors to assemble aspects of LC-MS/MS operations in the clinical laboratory to provide a framework for the thoughtful development and execution of LC-MS/MS applications.

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Simplification of Home Urine Sampling for Measurement of 2,8‐Dihydroxyadenine in Patients with Adenine Phosphoribosyltransferase Deficiency

Thorsteinsdottir,

Runolfsdottir,

Edvardsson

et al. 2023

Patient Centric Blood Sampling and Quantitative Bioanalysis

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Development and Validation of Small Molecule Analytes by Liquid Chromatography-Tandem Mass Spectrometry

Cited by 11 publications

References 38 publications

Review of the Use of Liquid Chromatography-Tandem Mass Spectrometry in Clinical Laboratories: Part I-Development

Review of the Use of Liquid Chromatography-Tandem Mass Spectrometry in Clinical Laboratories: Part I-Development

Review of the Use of Liquid Chromatography-Tandem Mass Spectrometry in Clinical Laboratories: Part II–Operations

Simplification of Home Urine Sampling for Measurement of 2,8‐Dihydroxyadenine in Patients with Adenine Phosphoribosyltransferase Deficiency

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