ICP-MS测定全血中5种微量元素及其参考区间的建立

doi:10.3969/j.issn.1673-8640.2018.02.008

摘要/Abstract

摘要：

目的建立同时测定全血中铁（Fe）、镁（Mg）、钙（Ca）、锌（Zn）、铜（Cu）的电感耦合等离子体质谱（ICP-MS）方法。方法将全血样本混匀后用含Triton 100的稀硝酸溶液进行50倍稀释,以锗（Ge）元素为内标,建立ICP-MS检测全血Fe、Mg、Ca、Zn、Cu的方法。收集495名体检健康者全血样本,按性别和年龄（≤16岁和>16岁）分别分组比较并建立5种元素的参考区间。结果 5种元素的标准曲线线性均良好（r值为0.999 6~1.000 0）,批内精密度为0.31%~3.62%,批间精密度为1.37%~7.15%,添加回收率为98.2%~112.7%。正常人群、男女性之间全血Fe、Mg、Ca、Zn、Cu水平差异均无统计学意义（P>0.05）,而≤16岁组与>16岁组之间5种元素差异均有统计学意义（P<0.05）。按年龄以x±2s方式建立参考区间：≤16岁者Mg为30.2~43.4 mg/L、Ca为47.2~69.6 mg/L、Fe为320.6~466.0 mg/L、Cu为0.64 ~1.36 mg/L、Zn为3.1~6.8 mg/L;>16岁者Mg为27.0~43.6 mg/L、Ca为42.6~64.6 mg/L、Fe为275.2~530.3 mg/L、Cu为0.40~1.58 mg/L、Zn为4.3~8.3 mg/L。结论建立的ICP-MS方法可同时测定Fe、Mg、Ca、Zn、Cu,敏感性高,操作简便、稳定,准确度高,可用于临床大样本分析。

关键词: 铁, 镁, 钙, 锌, 铜, 电感耦合等离子体质谱, 全血

Abstract:

Objective To establish an inductively coupled plasma mass spectrometry（ICP-MS） for the determinations of 5 kinds of trace elements [iron（Fe）,magnesium（Mg）,calcium（Ca）,zinc（Zn） and copper（Cu）] in whole blood. Methods After whole blood samples were fully mixed and diluted to 50 times with the solution containing Triton 100 and dilute nitric acid,adding germanium（Ge） as internal standard,an ICP-MS was established for determining 5 kinds of trace elements. A total of 495 whole blood samples of healthy subjects were collected. According to sex and age（≤16 years old and >16 years old groups）,the reference intervals were established. Results The standard curve linearities were good for 5 kinds of trace elements（r=0.999 6-1.000 0）. The within-run precision was 0.31%-3.62%,and the between-run precision was 1.37%-7.15%. The recovery rate was 98.2% -112.7 %. Each element had no statistical significance between males and females（P>0.05）,but there was statistical significance between ≤16 years old and >16 years old groups（P<0.05）. The reference intervals（x±2s） in ≤16 years old group were 30.2-43.4 mg/L for Mg,47.2-69.6 mg/L for Ca,320.6-466.0 mg/L for Fe,0.64 -1.36 mg/L for Cu and 3.1-6.8 mg/L for Zn,and those in >16 years old group were 27.0-43.6 mg/L,42.6-64.6 mg/L,275. 2-530.3 mg/L,0.40-1.58 mg/L and 4.3- 8.3 mg/L,respectively. Conclusions ICP-MS can determine Fe,Mg,Ca,Zn and Cu in whole blood simultaneously,with sensitivity,simple operation,stability and accuracy.

Key words: Iron, Magnesium, Calcium, Zinc, Copper, Inductively coupled plasma mass spectrometry, Whole blood

中图分类号:

Q581

徐凤仙, 于嘉屏, 吴娟娟. ICP-MS测定全血中5种微量元素及其参考区间的建立[J]. 检验医学, 2018, 33(2): 127-131.

XU Fengxian, YU Jiaping, WU Juanjuan. Determinations of 5 kinds of trace elements by ICP-MS and establishment of reference intervals[J]. Laboratory Medicine, 2018, 33(2): 127-131.

图/表 7

参考文献 16

[1]	CAI L,CHEN T,YANG J,et al.Serum trace element differences between Schizophrenia patients and controls in the Han Chinese population[J]. Sci Rep,2015,5:15013.
[2]	KOPRIVA D,KISHEEV A,MEENA D,et al.The nature of iron deposits differs between symptomatic and asymptomatic carotid atherosclerotic plaques[J]. PLoS One,2015,10(11):e0143138.
[3]	CRISTOVAO J S,SANTOS R,GOMES C M.Metals and neuronal metal binding proteins implicated in Alzheimer's disease[J]. Oxid Med Cell Longev,2016,2016:9812178.
[4]	TERRIN G,BERNI CANANI R,DI CHIARA M,et al.Zinc in early life:a key element in the fetus and preterm neonate[J]. Nutrients,2015,7(12):10427-10446.
[5]	傅银锋,闵玉芳,张一鸣,等. 难免流产胎儿微量元素的调查研究[J]. 检验医学,2006,21(3):219-221.
[6]	KHOUSHABI F,SHADAN M,MIRI A,et al.Determination of maternal serum zinc,iron,calcium and magnesium during pregnancy in pregnant women and umbilical cord blood and their association with outcome of pregnancy[J]. Mater Sociomed,2016,28(2):104-107.
[7]	蔡眉,唐振华,余文. 血锌、铁与血常规检测在儿童感染和贫血时的变化[J]. 检验医学,2014,29(11):1164-1168.
[8]	KRUGER P C,YANG K X,PARSONS P J,et al.Abundance and significance of iron,zinc,copper,and calcium in the hearts of patients with Friedreich ataxia[J]. Am J Cardiol,2016,118(1):127-131.
[9]	NICHOLS T A,SPRAKER T R,GIDLEWSKI T,et al.Dietary magnesium and copper affect survival time and neuroinflammation in chronic wasting disease[J]. Prion,2016,10(3):228-250.
[10]	GRIGORESCU R,GRUIA M I,NACEA V,et al.Parameters of oxidative stress variation depending on the concentration of inorganic zinc compounds[J]. J Med Life,2015, 8(4): 449-451.
[11]	谭昆,王书安,胡焰,等. 火焰原子吸收光谱法测定儿童全血中铁、锌、钙的浓度[J]. 中国医药导报,2012,9(5):112-113.
[12]	高岩,杨英,余波,等. 电感耦合等离子体发射光谱法测定正常人全血中铁、铜等10种元素[J]. 中国卫生检验杂志,2010,20(9):2149-2150.
[13]	李慧源,徐克前,汤郡. 电感耦合等离子质谱法检测儿童末梢血多种元素[J]. 国际检验医学杂志,2016,37(5):600-601.
[14]	覃珊,王焱,仰大贵,等. 儿童全血微量元素含量及补充现状调查[J]. 检验医学,2013,28(8):690-692.
[15]	肖钘,何金花,黎毓光,等. 广州市番禺区儿童全血5种微量元素检测结果分析[J]. 检验医学,2013,28(9):801-804.
[16]	杨华,卢建明,杨晓东,等. 1 100例18岁以下人群全血微量元素检测结果分析[J]. 国际检验医学杂志,2012,33(8):929-930.

项目	S1（mg/L）	S2（mg/L）	S3（mg/L）	S4（mg/L）	S5（mg/L）	LOQ（mg/L）	回归方程	r值
Fe	1.3	2.5	5.0	10.0	20.0	0.540	Y=0.277 035X	0.999 6
Mg	0.1	0.3	0.5	1.0	2.0	0.080	Y=0.119 425X	0.999 9
Ca	0.3	0.6	1.3	2.5	5.0	0.190	Y=0.020 273X	1.000 0
Zn	0.031 3	0.062 5	0.125	0.250	0.500	0.020	Y=2.571 633X	1.000 0
Cu	0.008	0.016	0.031	0.063	0.125	0.006	Y=0.024 439X	0.999 9

项目	S1（mg/L）	S2（mg/L）	S3（mg/L）	S4（mg/L）	S5（mg/L）	LOQ（mg/L）	回归方程	r值
Fe	1.3	2.5	5.0	10.0	20.0	0.540	Y=0.277 035X	0.999 6
Mg	0.1	0.3	0.5	1.0	2.0	0.080	Y=0.119 425X	0.999 9
Ca	0.3	0.6	1.3	2.5	5.0	0.190	Y=0.020 273X	1.000 0
Zn	0.031 3	0.062 5	0.125	0.250	0.500	0.020	Y=2.571 633X	1.000 0
Cu	0.008	0.016	0.031	0.063	0.125	0.006	Y=0.024 439X	0.999 9

项目	L1				L2
项目	C1（mg/L）	C2（mg/L）	C3（mg/L）	CV（%）	C1（mg/L）	C2（mg/L）	C3（mg/L）	CV（%）
Mg	0.5	0.52	0.49	2.27	1	1.01	0.98	1.58
Ca	1.25	1.28	1.26	1.09	2.5	2.46	2.47	0.85
Fe	5	4.86	5.27	4.18	10	9.96	10.12	0.86
Cu	0.031 3	0.032 2	0.032 1	1.55	0.063 0	0.062 5	0.062 1	0.74
Zn	0.13	0.13	0.14	5.99	0.25	0.26	0.27	3.1

项目	L1				L2
项目	C1（mg/L）	C2（mg/L）	C3（mg/L）	CV（%）	C1（mg/L）	C2（mg/L）	C3（mg/L）	CV（%）
Mg	0.5	0.52	0.49	2.27	1	1.01	0.98	1.58
Ca	1.25	1.28	1.26	1.09	2.5	2.46	2.47	0.85
Fe	5	4.86	5.27	4.18	10	9.96	10.12	0.86
Cu	0.031 3	0.032 2	0.032 1	1.55	0.063 0	0.062 5	0.062 1	0.74
Zn	0.13	0.13	0.14	5.99	0.25	0.26	0.27	3.1

项目	批内重复性			批间重复性
项目	低值	中值	高值	低值	中值	高值
Mg	1.79	1.28	0.31	2.87	1.52	1.37
Ca	2.9	2.31	1.25	5.58	1.76	1.63
Fe	3.07	1.31	1.64	2.39	2.66	2.24
Cu	2.82	0.88	0.35	7.15	2.47	2.03
Zn	3.62	1.99	1.72	6.99	1.59	1.43