Uma Sreenivasan (Presenter)
Bio: Uma Sreenivasan is Vice President R&D and Production Operations and Chief Scientist at Cerilliant Corporation. She is responsible for product development ranging from synthesis to solution standards. She has extensive experience in the fields of analytical and organic chemistry, NMR, and product design. She has worked in biomedical research and academic settings and has synthetic and analytical chemistry experience, project design and management, and process development experience.
Authorship: Uma Sreenivasan(1), Ravi Orugunty(1), Isil Dilek(1), Josh Cooper (1), Sarah Aijaz (1), Jackie Day(2), James J Walters(2), Kevin Ray(2)
1 – Cerilliant Corporation, 811 Paloma Dr., Round Rock, TX ; 2 – Sigma-Aldrich Corporation, Applied Research and Development, 2909 Laclede Ave., St. Louis MO
Accuracy based calibrators are critical for accurate quantitation of endogenous hormones, biomarkers and drugs in clinical diagnostics. Endogenous levels of analytes or impurities in serum and striped sera, can interfere with accuracy of low level calibrators. Stripped and synthetic matrices must also demonstrate commutability and performance equivalent to the endogenous matrix. High sensitivity LC-MS/MS and QTof procedures were developed for matrix screening and comparison . Synthetic matrices and stripped human sera were screened for use as calibration matrix for the quantitation of Testosterone. Critical performance requirements related to endogenous and extraneous interferences were identified and control strategies developed.
Accuracy based calibrators are critical for accurate quantitation of endogenous hormones, biomarkers and drugs in clinical diagnostics. The use of serum as a matrix for calibrators is complicated by endogenous levels of the analyte, especially in the development of low level calibrators. Alternatives such as stripped and synthetic matrices must demonstrate commutability and performance equivalent to the endogenous matrix.
Matrix selection and performance of the matrix based calibrator is analyte and assay specific. High sensitivity LCMS/MS and QTof MS methods were used to characterize synthetic matrices and stripped human sera. Methods were developed to screen matrices for Testosterone calibrators across a wide dynamic range from 20 pg/mL to 20 ng/mL. Quantitation of endogenous testosterone required further optimization to quantitate residual testosterone in the matrix. QTof screening of impurity profiles was critical to optimization and selection of the matrix and is a valuable tool in development of robust calibrators. QTof analysis of interferences provided insight into impurity identity and potential interferences.
Accurate quantitation of residual testosterone in stripped serum was critical for accuracy of the calibrators. Quantitation methods for matrix selection were optimized for quantitation to <2 pg/mL.
References & Acknowledgements:
|Salary||yes||Cerilliant Corporation (Employee of )|
IP Royalty: no
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