Leonard Michael, Dunn John, Smith Glenn
GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
Bioanalysis. 2014 Mar;6(6):745-59. doi: 10.4155/bio.13.323.
Current methods to measure skeletal muscle mass are not practical in a clinical setting. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods that measure the amount of urinary d3-creatinine enrichment after a single tracer dose of d3-creatine was developed.
The biomarkers d3-creatinine and creatinine were detected in human urine using LC-MS/MS. In this assay a surrogate analyte, d3-creatinine, was used to quantify endogenous creatinine. However, since endogenous concentrations of creatinine were orders of magnitude higher than d3-creatinine, the peak area of a less intense isotope of creatinine was acquired. A response factor is used to correct for using a less intense isotope multiple reaction monitoring transition.
Novel LC-MS/MS assays were developed that quantify the biomarkers d3-creatinine, creatinine and d3-creatine in urine. This method allows the estimation of total body creatine pool size and subsequent calculation of muscle mass. This assay was originally validated as fit-for-purpose and was followed by full validation.
目前测量骨骼肌质量的方法在临床环境中并不实用。已开发出液相色谱 - 串联质谱（LC-MS/MS）方法，该方法在单次给予示踪剂量的d3-肌酸后测量尿中d3-肌酐富集量。
使用LC-MS/MS在人尿中检测到生物标志物d3-肌酐和肌酐。在该分析中，使用替代分析物d3-肌酐来定量内源性肌酐。然而，由于内源性肌酐浓度比d3-肌酐高几个数量级，因此获取了强度较低的肌酐同位素的峰面积。使用响应因子来校正使用强度较低的同位素多反应监测转变。
开发了新型LC-MS/MS分析方法来定量尿中的生物标志物d3-肌酐、肌酐和d3-肌酸。该方法允许估计全身肌酸池大小并随后计算肌肉质量。该分析最初经验证符合用途，随后进行了全面验证。
