scholarly journals Total and Exchangeable Copper Assay Using Inductively Coupled Plasma Mass Spectrometry and Establishment of a Pediatric Reference Interval

Author(s):  
Jisook Yim ◽  
Soo Beom Kwon ◽  
Jung Sun Han ◽  
Jeong-Ho Kim ◽  
Eun Hee Lee ◽  
...  

Context.— Recently, an exchangeable copper (CuEXC) assay has been suggested as a robust and feasible diagnostic tool for Wilson disease (WD). Although WD is a disorder that requires lifelong treatment and monitoring, few data are currently available regarding the status of copper levels in children. Objective.— To evaluate the performance of copper assays and establish a reference interval for total copper and CuEXC in the pediatric population. Design.— Serum samples from children aged 1–5 (n = 122), 6–12 (n = 125), and 13–18 years (n = 120) were analyzed. Total copper and CuEXC concentrations were directly measured using inductively coupled plasma mass spectrometry, and relative CuEXC levels were calculated. Total copper reference intervals, CuEXC levels, and relative CuEXC levels were determined based on the 2.5th and 97.5th percentiles of the data with 90% confidence intervals. Results.— There were significant differences in the median concentrations of total copper and relative CuEXC among the age groups. Reference intervals determined for total copper were 82 to 167, 75 to 139, and 64 to 133 μg/dL for children aged 1 to 5, 6 to 12, and 13 to 18 years, respectively. The reference intervals for CuEXC were 4.29 to 9.79, 4.02 to 9.09, and 3.55 to 8.25 μg/dL for children aged 1 to 5, 6 to 12, and 13 to 18 years, respectively. Among 11 patients with suspected WD, relative CuEXC values were elevated in all 3 diagnosed with WD. Conclusions.— The pediatric reference intervals derived in this study are expected to be useful for the diagnosis, differential diagnosis, treatment, and monitoring of pediatric patients with WD.

Author(s):  
P Wainwright ◽  
D Wadey ◽  
P Cook

Background Diagnosis of Wilson’s disease is currently performed using caeruloplasmin as a first-line screening test; however, this test has well-described limitations. Monitoring of known Wilson’s disease patients often uses 24-h urine collection; however, this is inaccurate in children. Methods for directly measuring plasma free copper have been described, but no reference interval data exist for a paediatric population. Methods An inductively coupled plasma mass spectrometry method for measuring free copper was developed and validated, using ultracentrifugation. A paediatric reference interval was generated using 85 plasma samples from children attending outpatient clinics at University Hospital Southampton. Results Results showed no significant contamination of copper using the ultracentrifugation technique, and validation showed the method was accurate and precise with an analytical coefficient of variation between 5 and 7% depending on the concentration of free copper. Conclusions We describe the use and validation of an ultrafiltration inductively coupled plasma mass spectrometry method for plasma free copper with the first published paediatric reference interval. Free copper could provide much needed assistance for the monitoring of Wilson’s disease in children and also for adults.


Author(s):  
Xiaoyu Fan ◽  
Qing Li ◽  
Ping Lin ◽  
Zhonggan Jin ◽  
Meizi Chen ◽  
...  

Background Therapeutic monitoring of lithium (Li) is important because of its narrow therapeutic range and therapeutic index. Here, the authors present the evaluation of an accurate method for the determination of lithium in serum. Method Serum samples were diluted with 0.3% ultrapure nitric acid and were spiked with an internal standard germanium (Ge). The Li/Ge ratio was detected in He mode; we utilized standard addition method to quantify lithium in human serum. The new inductively coupled plasma mass spectrometry (ICP-MS) assay was characterized for linearity, specificity, imprecision, trueness, accuracy, and comparison. Results The correlation coefficients (r) of linearity were all > 0.9999. The specificity proved to be good. The total coefficients of variation (CV) were 1.11% and 0.49% for the two serum samples. The mean bias from target values of standard reference materials (SRM 956d) was −0.71% for Level I, −017% for Level II, and 2.20 for Level III. External Quality Assessment Scheme for Reference Laboratories in Laboratory Medicine (RELA) gave satisfied results for the new method. Comparison with the ion-selective electrode routine method got reasonable results. Conclusion This high accuracy method is an attractive alternative for lithium measurement and can be used as a candidate reference method to improve quality of serum lithium in China.


2017 ◽  
Vol 55 (10) ◽  
Author(s):  
Ying Yan ◽  
Bingqing Han ◽  
Jie Zeng ◽  
Weiyan Zhou ◽  
Tianjiao Zhang ◽  
...  

AbstractBackground:Potassium is an important serum ion that is frequently assayed in clinical laboratories. Quality assurance requires reference methods; thus, the establishment of a candidate reference method for serum potassium measurements is important.Methods:An inductively coupled plasma mass spectrometry (ICP-MS) method was developed. Serum samples were gravimetrically spiked with an aluminum internal standard, digested with 69% ultrapure nitric acid, and diluted to the required concentration. TheResults:The correlation coefficients between the measuredConclusions:The new ICP-MS method is specific, precise, simple, and low-cost, and it may be used as a candidate reference method for standardizing serum potassium measurements.


Author(s):  
Bingqing Han ◽  
Menglei Ge ◽  
Haijian Zhao ◽  
Ying Yan ◽  
Jie Zeng ◽  
...  

Abstract: Serum calcium level is an important clinical index that reflects pathophysiological states. However, detection accuracy in laboratory tests is not ideal; as such, a high accuracy method is needed.Methods:We developed a reference method for measuring serum calcium levels by isotope dilution inductively coupled plasma mass spectrometry (ID ICP-MS), usingResults:The relative expanded uncertainty of the sample concentration was 0.414% (k=2). The range of repeatability (within-run imprecision), intermediate imprecision (between-run imprecision), and intra-laboratory imprecision were 0.12%–0.19%, 0.07%–0.09%, and 0.16%–0.17%, respectively, for two of the serum samples. SRM909bI, SRM909bII, SRM909c, and GBW09152 were found to be within the certified value interval, with mean relative bias values of 0.29%, −0.02%, 0.10%, and −0.19%, respectively. The range of recovery was 99.87%–100.37%. Results obtained by ID ICP-MS showed a better accuracy than and were highly correlated with those of other reference methods.Conclusions:ID ICP-MS is a simple and accurate candidate reference method for serum calcium measurement and can be used to establish and improve serum calcium reference system in China.


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