Over the past few years, stable labeled isotopes (SILs) have played a critical role in bio-analysis, nearly replacing the use of structural analogues as internal standards. SILs are now the first choice of researchers/chemists when selecting an internal standard for day-to-day analysis to avoid process and analytical variation. However, although SILs are widely used in analytical labs today, they have challenging issues, such as the matrix effect, recovery, and ionization problems. The purpose of this review is to brief about both advantages and disadvantages of stable label internal standards from recent publications. Despite of having SILs in analytical methodology chemists observed the method issues and these were resolved later by replacing with structure analogs in their methodology.
Background: This article describes the development and validation of a bioanalytical assay to quantify CPI-613 and its major metabolites, CPI-2850 and CPI-1810, in human plasma matrix using LC-MS/MS. Methodology: Sample extraction procedure following protein precipitation with acetonitrile was optimized to extract all three analytes from plasma with maximum recovery. The final extracted supernatants were diluted with water and injected onto an Xbridge C18 (50 × 2.1 mm; 5 μm) column for analysis. The analytes were separated by a gradient elution, and detection was performed on a triple quadrupole mass spectrometer (Sciex API 5000) operating in the negative ion mode. Results: The assay was linear over a range of 50–50,000 ng/ml for CPI-613, 250–250,000 ng/ml for CPI-2850 and 10–10,000 ng/ml for CPI-1810. Benchtop stability was established for 24 h, and four freeze–thaw cycles were evaluated for CPI-613 and its metabolites. Long-term freezer (-60 to -80°C) stability for about 127 days was established in this validation. Mean matrix recovery was more than 80% for all analytes. Conclusion: A robust LC-MS/MS method was developed for the quantification of CPI-613 and its major metabolites. The current assay will be used to support ongoing and future CPI-613 clinical trials.
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