Norman Hardt (Presenter)
Merck Group
Authorship: Norman Hardt (1), Linda Nagore (2), Ravi Orugunty (2), Sarah Aijaz (2), Isil Dilek (2) and Uma Sreenivasan (2)
(1) Sigma-Aldrich Chemie GmbH, Buchs, Switzerland (2) Cerilliant Corporation, Round Rock, United States of America
| Short Abstract Development of accuracy-based calibrators in biological matrices for clinical diagnostic applications requires reference measurement calibrators and materials with high accuracy and sensitivity. A method for in vitro diagnostic (IVD) use in LC-MS/MS-based laboratory developed tests (LDTs) for quantitation of testosterone across the entire therapeutic range from 2-2,000 ng/dL in serum by Liquid Chromatography Mass Spectrometry (LC-MS/MS) was developed and validated. A certified reference material (CRM) grade serum calibrant kit, designed to bracket male and female testosterone clinical reference ranges, including 10 levels from 2-2,000 ng/dL along with a blank and 13C-labeled internal standard was developed and validated towards stability under various storage conditions. |
Long Abstract
Development of accuracy-based calibrators in biological matrices for clinical diagnostic applications requires reference measurement calibrators and materials with high accuracy and sensitivity. Testosterone presents a unique challenge with the wide range of endogenous levels across female, male and age-based patient populations. Most circulating testosterone is bound to sex hormone-binding globulin (SHBG), which in men is also called testosterone-binding globulin. Clinical assessment of testosterone levels in males and females is performed for a variety of diagnostic applications including evaluation of men with symptoms or signs of possible hypogonadism, monitoring of testosterone therapy or antiandrogen therapy and diagnosis of androgen-secreting tumors, between others.[1]
Recent literature reports that reference ranges as well as the methodology to develop reference ranges for testosterone assays can vary significantly among laboratories. According to these studies, variation in testosterone results may be due to underutilization among laboratories to develop testosterone reference ranges specific to clinical populations and potential limited use of a serum-based specimen calibration program.[2]
Within this study we present the development and evaluation of a method for in vitro diagnostic (IVD) use in LC-MS/MS-based laboratory developed tests (LDTs) for quantitation of testosterone across the entire therapeutic range from 2-2,000 ng/dL in serum by Liquid Chromatography Mass Spectrometry (LC-MS/MS). A certified reference material (CRM) grade serum testosterone calibrant kit, designed to bracket male and female testosterone clinical reference ranges, including 10 levels from 2-2,000 ng/dL along with a blank and 13C-labeled internal standard was developed and validated towards stability under various storage conditions.
In conclusion we developed and tested a CRM grade testosterone calibrator kit in stripped serum that is prepared and tested to the highest industry standards for quantitation of testosterone across the entire therapeutic range. The testosterone serum calibrator is affixed with a CE mark, demonstrating that it conforms to the in vitro diagnostic (IVD) Medical Device Directive (98/79/EC) for availability in Europe.
References & Acknowledgements:
[1] a) Oliver T. Wolf and Clemens Kirschbaum, Hormones and Behavior, 2002, 41, 259-266. b) S. Mitchell Harman, E. Jeffrey Metter, Jordan D. Tobin, Jay Pearson and Marc R. Blackman, The Journal of Clinical Endocrinology and Metabolism, 2000, 86, 724-731. c) G. Schatzl, S. Madersbacher, T. Thurridl, J. Waldmüller, G. Kramer, A. Haitel and M. Marberger, Prostate, 2001, 47, 52-58.
[2] a) Le Margaret, David Flores, Danica May, Eric Gourley and Ajay K. Nangia, The Journal of Urology, 2016, 5, 1556-1561. b) Tobias S.Köhler, The Journal of Urology, 2016, 5, 1561.
| Description | Y/N | Source |
| Grants | no | |
| Salary | yes | Merck Group |
| Board Member | no | |
| Stock | no | |
| Expenses | no |
IP Royalty: no
| Planning to mention or discuss specific products or technology of the company(ies) listed above: | yes |