Affiliation:
1. Dr. Risch Ostschweiz AG , Buchs , Switzerland
2. Roche Diagnostics GmbH , Penzberg , Germany
3. Chrestos Concept GmbH & Co. KG , Essen , Germany
Abstract
Abstract
Objectives
To describe and validate a reference measurement procedure (RMP) for gabapentin, employing quantitative nuclear magnetic resonance (qNMR) spectroscopy to determine the absolute content of the standard materials in combination with isotope dilution-liquid chromatograph-tandem mass spectrometry (ID-LC-MS/MS) to accurately measure serum and plasma concentrations.
Methods
A sample preparation protocol based on protein precipitation in combination with LC-MS/MS analysis using a C8 column for chromatographic separation was established for the quantification of gabapentin. Assay validation and determination of measurement uncertainty were performed according to guidance from the Clinical and Laboratory Standards Institute, the International Conference on Harmonization, and the Guide to the expression of uncertainty in measurement. ID-LC-MS/MS parameters evaluated included selectivity, specificity, matrix effects, precision and accuracy, inter-laboratory equivalence, and uncertainty of measurement.
Results
The use of qNMR provided traceability to International System (SI) units. The chromatographic assay was highly selective, allowing baseline separation of gabapentin and the gabapentin-lactam impurity, without observable matrix effects. Variability between injections, preparations, calibrations, and days (intermediate precision) was <2.3%, independent of the matrix, while the coefficient of variation for repeatability was 0.9–2.0% across all concentration levels. The relative mean bias ranged from −0.8–1.0% for serum and plasma samples. Passing-Bablok regression analysis indicated very good inter-laboratory agreement; the slope was 1.00 (95% confidence interval [CI] 0.98 to 1.03) and the intercept was −0.05 (95% CI -0.14 to 0.03). Pearson’s correlation coefficient was ≥0.996. Expanded measurement uncertainties for single measurements were found to be ≤5.0% (k=2).
Conclusions
This analytical protocol for gabapentin, utilizing traceable and selective qNMR and ID-LC-MS/MS techniques, allows for the standardization of routine tests and the reliable evaluation of clinical samples.
Subject
Biochemistry (medical),Clinical Biochemistry,General Medicine
Reference44 articles.
1. Wallach, JD, Ross, JS. Gabapentin approvals, off-label use, and lessons for postmarketing evaluation efforts. JAMA 2018;319:776–8. https://doi.org/10.1001/jama.2017.21897.
2. Pfizer Inc. Gabapentin (Neurontin). Highlights of prescribing information; 2022. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/020235s064_020882s047_021129s046lbl.pdf.
3. Cooper, TE, Derry, S, Wiffen, PJ, Moore, RA. Gabapentin for fibromyalgia pain in adults. Cochrane Database Syst Rev 2017;1:Cd012188. https://doi.org/10.1002/14651858.CD012188.pub2.
4. Goodman, CW, Brett, AS. A clinical overview of off-label use of gabapentinoid drugs. JAMA Intern Med 2019;179:695–701. https://doi.org/10.1001/jamainternmed.2019.0086.
5. Kumar, AH, Habib, AS. The role of gabapentinoids in acute and chronic pain after surgery. Curr Opin Anaesthesiol 2019;32:629–34. https://doi.org/10.1097/aco.0000000000000767.
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献