A validated LC-MS/MS method for the quantitative measurement of creatinine as an endogenous biomarker in human plasma.
BACKGROUND
Creatinine is an endogenous compound generated from creatine by normal muscular metabolism. It is an important indicator of renal function and the serum level is routinely monitored in clinical labs. Results & methodology: Surrogate analyte (d3-creatinine) was used for calibration standard and quality control preparation and the relative instrument response ratio between creatinine and d3-creatinine was used to calculate the endogenous creatinine concentrations.


CONCLUSIONS
A fit-for-purpose strategy of using a surrogate analyte and authentic matrix was adopted for this validation. The assay was the first human plasma assay using such strategy and was successfully applied to a clinical study to confirm a transient elevation of creatinine observed using an existing clinical assay.
Analytical & Bioanalytical Operations, Research & Development, Bristol-Myers Squibb Co., Rt 206 & Provinceline Rd, Princeton, NJ 08543, USA.
Yue
Y
Zhao
DMPK-Clinical Bioanalytical, Agios Pharmaceuticals, 88 Sidney Street, Cambridge, MA 02139, USA.
Guowen
G
Liu
Analytical & Bioanalytical Operations, Research & Development, Bristol-Myers Squibb Co., Rt 206 & Provinceline Rd, Princeton, NJ 08543, USA.
Aida
A
Angeles
Department of Biotransformation, Research & Development, Bristol-Myers Squibb Co., Rt 206 & Provinceline Rd, Princeton, NJ 08543, USA.
Lisa J
LJ
Christopher
Early Clinical & Translational Research, Research & Development, Bristol-Myers Squibb Co., 311 Pennington-Rocky Hill Rd, Pennington, NJ 08534, USA.
Zhaoqing
Z
Wang
Analytical & Bioanalytical Operations, Research & Development, Bristol-Myers Squibb Co., Rt 206 & Provinceline Rd, Princeton, NJ 08543, USA.
Mark E
ME
Arnold
Analytical & Bioanalytical Operations, Research & Development, Bristol-Myers Squibb Co., Rt 206 & Provinceline Rd, Princeton, NJ 08543, USA.
Jim X
JX
Shen
D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis / Q000379:methods*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000592:standards; D003404:Creatinine / Q000097:blood* / Q000737:chemistry / Q000592:standards; D006801:Humans; D011786:Quality Control; D053719:Tandem Mass Spectrometry / Q000592:standards
D015415:Biomarkers; D003404:Creatinine
LC–MS/MS; endogenous biomarker; fit-for-purpose validation; surrogate analyte