Department of Pharmacology and Clinical Pharmacology, Christian Medical College, Vellore, Tamil Nadu, India.
Department of Pharmacology and Clinical Pharmacology, Christian Medical College, Vellore, Tamil Nadu, India.
Clin Biochem. 2022 Jul-Aug;105-106:25-34. doi: 10.1016/j.clinbiochem.2022.04.014. Epub 2022 Apr 28.
Serial monitoring of tacrolimus and serum creatinine after renal transplantation is of vital importance. In this study, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for the estimation of tacrolimus and creatinine, obtained from dried blood spots (DBS) or by volumetric absorptive microsampling (VAMS) was validated and the two sampling strategies were compared with traditional venous sampling.
The LC-MS/MS assay was validated using a shared extract for the estimation of tacrolimus and creatinine from DBS and VAMS independently. The relationship between the concentrations in DBS/VAMS specimens and in venous samples was assessed using Passing-Bablok (PB) analysis and the bias between the two methods was determined by the Bland Altman (BA) analysis.
The imprecision and bias of tacrolimus and creatinine estimated from DBS and VAMS samples was <12% and was independent of the hematocrit (Hct). Samples were stable for five days at ambient temperature. From the PB regression analysis, correction equations were generated for the prediction of tacrolimus and creatinine values from DBS and VAMS samples. In a separate cohort of patients for validation, the corrected DBS and VAMS concentrations had a mean (95% CI) bias for tacrolimus of -0.64 (-2.98 to 1.70)% and -0.92 (-3.69 to 1.85)% respectively and for creatinine of 1.00 (-2.73 to 4.72)% and -0.71 (-3.74 to 2.32)% respectively. Using DBS and VAMS respectively, for tacrolimus, 91.8 and 89.8% of patient values and for creatinine, 69.4 and 81.6% of patient values were within the limits of clinical acceptance (within 15% agreement against the venous samples).
We conclude that VAMS is the preferred single sampling option for estimating tacrolimus and creatinine in renal transplant patients.
肾移植后对他克莫司和血清肌酐进行连续监测至关重要。本研究建立了一种通过测定干血斑（DBS）或体积吸收微采样（VAMS）标本中的他克莫司和肌酐浓度，来评估肾移植患者他克莫司和肌酐浓度的液相色谱-串联质谱（LC-MS/MS）检测方法，并比较了两种采样策略与传统静脉采样的差异。
采用共享提取法，分别对 DBS 和 VAMS 标本中的他克莫司和肌酐进行定量分析，验证 LC-MS/MS 检测方法的准确性。采用 Passing-Bablok（PB）回归分析法评估 DBS/VAMS 标本浓度与静脉标本浓度之间的相关性，采用 Bland-Altman（BA）分析法评估两种方法之间的偏差。
DBS 和 VAMS 标本中他克莫司和肌酐的精密度和偏差均<12%，且与红细胞压积（Hct）无关。室温下，样本在 5 天内稳定。通过 PB 回归分析，建立了 DBS 和 VAMS 样本中他克莫司和肌酐预测值的校正方程。在另一组患者的验证队列中，DBS 和 VAMS 校正浓度的平均（95%CI）偏倚分别为他克莫司-0.64%（-2.98 至 1.70%）和-0.92%（-3.69 至 1.85%），肌酐为 1.00%（-2.73 至 4.72%）和-0.71%（-3.74 至 2.32%）。分别使用 DBS 和 VAMS 测定他克莫司时，91.8%和 89.8%的患者值，以及测定肌酐时，69.4%和 81.6%的患者值在临床可接受范围内（与静脉样本的偏差<15%）。
我们得出结论，VAMS 是评估肾移植患者他克莫司和肌酐的首选采样方法。
