《SN∕T 5324.3-2020 出口包装饮用水和饮用天然矿泉水中扑尔敏、西咪替丁、异丙嗪、苯海拉明、雷尼替丁、阿替洛尔、普萘洛尔和沙丁胺醇的测定 液相色谱-质谱法(出入境检验检疫).pdf》由会员分享，可在线阅读，更多相关《SN∕T 5324.3-2020 出口包装饮用水和饮用天然矿泉水中扑尔敏、西咪替丁、异丙嗪、苯海拉明、雷尼替丁、阿替洛尔、普萘洛尔和沙丁胺醇的测定 液相色谱-质谱法(出入境检验检疫).pdf（20页珍藏版）》请在taowenge.com淘文阁网|工程机械CAD图纸|机械工程制图|CAD装配图下载|SolidWorks_CaTia_CAD_UG_PROE_设计图分享下载上搜索。
1、中华人民共和国出入境检验检疫行业标准SN/T 5324.32020出口包装饮用水和饮用天然矿泉水中扑 尔敏、西咪替丁、异丙嗪、苯海拉明、雷尼替丁、阿替洛尔、普萘洛尔和沙丁 胺醇的测定 液相色谱-质谱/质谱法Determination of chlorpheniramine,cimetidine,promethazine,diphenhydramine,ranitidine,atenolol,propranolol and salbutamol in exported packaged water and drinking natural mineral water LC-MS/MS metho
2、d2020-12-30 发布2021-07-01 实施ICS 67.160CCS X 51中华人民共和国海关总署发 布SN/T 5324.32020I前 言本文件按照 GB/T 1.1 2009、GB/T 20001.4 2001 和 SN/T 0001 2016 的规则编写。请注意本文件的某些内容可能涉及专利。本文件的发布机构不承担识别这些专利的责任。本文件由中华人民共和国海关总署提出并归口。本文件起草单位：中华人民共和国北京海关、北京市食品科学研究院、中华人民共和国黄岛海关、中国人民解放军疾病预防控制中心。本部分主要起草人：刘萤、梁娜娜、王珮玥、韩深、齐鹤鸣、古瑾、崔凤云、冯鑫、郭庆龙、张
3、灿。1SN/T 5324.32020出口包装饮用水和饮用天然矿泉水中扑 尔敏、西咪替丁、异丙嗪、苯海拉明、雷尼替丁、阿替洛尔、普萘洛尔和沙丁 胺醇的测定 液相色谱-质谱/质谱1 范围 本文件规定了饮用纯净水、饮用天然矿泉水和其他饮用水中扑尔敏、西咪替丁、异丙嗪、苯海拉明、雷尼替丁、阿替洛尔、普萘洛尔和沙丁胺醇测定的液相色谱-质谱/质谱法。本文件适用于饮用纯净水、饮用天然矿泉水和其他饮用水中扑尔敏、西咪替丁、异丙嗪、苯海拉明、雷尼替丁、阿替洛尔、普萘洛尔和沙丁胺醇的测定。2 规范性引用文件下列文件中的内容通过文中的规范性引用而构成本文件必不可少的条款。其中，注日期的引用文件，仅该日期对应的版本适
4、用于本文件；不注日期的引用文件，其最新版本（包括所有的修改单）适用于本文件。GB/T 33087 仪器分析用高纯水规格及试验方法。3 术语和定义本文件没有需要界定的术语和定义。4 方法提要样品中的待测物质直接通过液相色谱-串联质谱仪进行分离和测定，外标法定量。5 试剂和材料除另有说明外，所用试剂均为色谱纯，水应为符合 GB/T 33087 规定的仪器分析用高纯水的要求。5.1 甲醇。5.2 甲酸。5.3 乙腈。5.4 0.5%甲酸：5 mL 甲酸溶解于水中，并定容至 1 L。5.5 20%甲醇：20 mL 甲醇溶解于水中，并定容至 100 mL。5.6 阿替洛尔标准物质：C14H22N2O3，
5、CAS 29122-68-7，纯度 99%。5.7 普萘洛尔标准物质：C16H21NO2.，CAS 525-66-6，纯度 99%。5.8 沙丁胺醇标准物质：C13H21NO3，CAS 18559-94-9，纯度 99%。5.9 扑尔敏标准物质：C20H23ClN2O4，CAS 113-92-8，纯度 99%。2SN/T 5324.320205.10 西咪替丁标准物质：C10H16N6S，CAS 51481-61-9，纯度 99%。5.11 异丙嗪标准物质：C17H20N2S，CAS 60-87-7，纯度 99%。5.12 苯海拉明标准物质：C17H21NO，CAS 58-73-1，纯度 99
6、%。5.13 雷尼替丁标准物质：C13H22N4O3S，CAS 66357-35-5 纯度 99%。5.14 标准物质储备溶液：分别准确称取标准物质阿替洛尔（5.6）、普萘洛尔（5.7）、沙丁胺醇（5.8）、扑尔敏（5.9）、西咪替丁（5.10）、异丙嗪（5.11）、苯海拉明（5.12）、雷尼替丁（5.13）标准物质各10.0mg（精确至 0.1mg）于 10 mL 棕色容量瓶中，分别用甲醇（5.1）溶解并定容至刻度，配制成浓度为 1 000 mg/L 的标准储备液，于-18避光保存。5.15 混合标准中间溶液：分别取标准储备液（5.14）0.1 mL，混合后用甲醇（5.1）定容于 10 mL
7、 容量瓶，配制成浓度为 10 mg/L 的混合标准中间溶液，于 4避光保存。5.16 混合标准工作溶液：准确移取适量的混合标准中间溶液（5.15），用 20%甲醇（5.5）稀释成0.05 ng/mL、0.1ng/mL、0.2 ng/mL、0.5 ng/mL、2 ng/mL、10 ng/mL、25 ng/mL、40 ng/mL 浓度水平的混合标准工作溶液，摇匀，使用前配制。6 仪器和设备6.1 高效液相色谱质谱/质谱仪:配有电喷雾离子源（ESI）。6.2 天平：感量为 0.1 mg。6.3 高速离心机：转速 10 000 r/min。6.4 具塞塑料离心管：2 mL。6.5 尼龙微孔滤膜：0.2
8、2 mm7 测定步骤7.1 试样的制备将水样摇匀静置 10 min 后，量取适量水样至具塞塑料离心管（5.4）中，于 12 000 r/min 离心 5 min 后，取上清液过尼龙微孔滤膜（5.5）于进样小瓶中，待分析。7.2 试样的保存将试样于 4内避光保存。7.3 测定7.3.1 液相色谱参考条件液相色谱参考条件如下：a）流动相（A）：乙腈；流动相（B）：0.5%甲酸水溶液；b）色谱柱：UPLC BEH C18（2.1 100 mm，1.7 m）柱；或同等性能的色谱柱。c）流速：0.35 mL/min；d）进样量：5 L；e）柱温：40 ；f）梯度洗脱：见表 1。3SN/T 5324.32
9、020表 1 液相梯度洗脱程序时间/（min）%A%B0.05.0 95.0 0.55.0 95.0 3.030.0 70.0 9.095.0 5.0 10.095.0 5.0 10.55.0 95.0 12.05.0 95.0 7.3.2 质谱参考条件质谱参考条件如下：a）离子化模式：电喷雾离子源（ESI+）；b）扫描方式：多反应监测模式（MRM）c）使用前应调节各参数使质谱灵敏度达到检测要求，参考条件参见附录 A。7.3.3 定性测定按照液相色谱-质谱/质谱条件测定样品和标准工作溶液，如果检测的质量色谱峰保留时间与标准品保留时间相差不超过 5%，定性离子对相对丰度（是用相对于最强离子丰度的
10、强度百分比表示）与浓度相当的标准工作溶液的相对丰度一致，相对丰度允许偏差不超过表 2 规定的范围，则可判定样品中存在对应的待测物。表 2 定性确证时相对离子丰度的最大允许偏差相对离子丰度/%5020501020 10允许的最大偏差/%202530507.3.4 定量测定根据试样中被测物的含量情况，选取响应值相近的标准工作液一起进行色谱分析。标准工作液和待测液中扑尔敏、西咪替丁、异丙嗪、苯海拉明、雷尼替丁、阿替洛尔、普萘洛尔和沙丁胺醇的响应值应在仪器线性响应范围内。样品溶液中的参考保留时间见附录 A。扑尔敏、西咪替丁、异丙嗪、苯海拉明、雷尼替丁、阿替洛尔、普萘洛尔和沙丁胺醇的标准物质多反应监测（
11、MRM）色谱图参见附录 B。7.3.5 空白试验用水代替样品，按上述操作步骤进行。8 结果计算和表述出口瓶装水和饮用水中扑尔敏、西咪替丁、异丙嗪、苯海拉明、雷尼替丁、阿替洛尔、普萘洛4SN/T 5324.32020尔和沙丁胺醇的测定结果按照式（1）计算。用色谱数据处理器或者按照式（1）计算试样中被检测物的残留含量，计算结果需扣除空白：Xi=cif（1）式中：Xi试样中待测物的残留量，单位为纳克每升（ng/mL）；ci 试样溶液中待测物质的浓度，单位为纳克每毫升（ng/mL）；f 样品的稀释倍数。计算结果保留三位有效数字。9 方法的定量限和回收率9.1 定量限饮用纯净水、饮用天然矿泉水和其他饮用
12、水中扑尔敏、西咪替丁、异丙嗪、苯海拉明、雷尼替丁、阿替洛尔、普萘洛尔和沙丁胺醇测定的定量限均为 0.05 ng/mL。9.2 回收率出口瓶装水和饮用水中扑尔敏、西咪替丁、异丙嗪、苯海拉明、雷尼替丁、阿替洛尔、普萘洛尔和沙丁胺醇的添加水平和回收率数据见表 3。表 3 出口瓶装水和饮用水中扑尔敏、西咪替丁、异丙嗪、苯海拉明、雷尼替丁、阿替洛尔、普萘洛尔和沙丁胺醇的的添加水平和回收率范围（n=6）化合物添加水平 ng/mL回收率范围（%）饮用纯净水饮用天然矿泉水其他饮用水阿替洛尔0.0589.8-96.785.2-91.793.7-106.90.194.5-105.784.0-103.296.7-1
13、07.60.593.1-105.686.3-93.789.2-95.7普萘洛尔0.0588.0-101.882.0-93.384.4-90.40.187.0-92.785.5-108.983.2-91.10.592.0-96.4104.8-107.395.3-107.1沙丁胺醇0.0595.5-100.395.4-106.484.9-107.20.187.0-98.381.3-92.994.7-109.70.584.1-93.295.1-102.890.0-94.6扑尔敏0.0586.6-98.586.6-95.696.2-109.60.182.8-109.196.0-103.691.7-10
14、0.80.583.2-95.895.0-108.186.9-94.9西咪替丁0.0599.7-103.484.3-100.395.8-101.10.193.2-105.681.6-94.794.7-102.10.580.3-100.081.3-90.985.4-88.75SN/T 5324.32020表 3（续）化合物添加水平 ng/mL回收率范围（%）饮用纯净水饮用天然矿泉水其他饮用水异丙嗪0.0596-107.594.7-106.381.4-96.60.184.2-96.680.4-96.083.9-91.30.588.7-92.183.5-99.090.8-100.8苯海拉明0.0593
15、.4-101.994.7-104.186.8-91.30.184.0-93.482.7-98.795.0-108.80.598.1-105.986.3-98.980.1-99.8雷尼替丁0.0580.4-91.882.1-101.781.5-98.40.184.9-96.197.2-101.283.8-90.70.5103.5-109.294.1-105.286.8-97.16SN/T 5324.32020附 录 A（资料性）质谱参数1）A.1 液相色谱-质谱/质谱参数如下：a）毛细管电压：1.00 kV；b）去溶剂气温度：500 ；c）去溶剂气流速：1000 L/Hr；d）碰撞气流速：0.1
16、4 mL/min；e）离子源温度：150 ；f）雾化气压力：6.0 bar。g）定性定量离子和优化的锥孔电压和碰撞能量参见表 A.1。表 A.1 主要质谱参数化合物 保留时间母离子 m/z子离子 m/z锥孔电压（V）碰撞电压（ev）阿替洛尔2.15267.2 145.1*4025190.14020普萘洛尔4.68260.3183.0*1023116.11019沙丁胺醇2.08240.2148.1*3020222.13012扑尔敏3.55275.1167.0*2038201.22034西咪替丁2.14253.1159.1*3015117.13015异丙嗪5.81285.286.1*2515198
17、.12525苯海拉明5.22256.1167.1*205152.02030雷尼替丁2.18315.2176.1*2515130.12525注:带*的离子为定量离子。1）非商业性声明：附录 A 所列参数是在 Waters Xevo TQ-S 质谱仪上完成的，此处列出试验用仪器型号仅是为了提供参考，并不涉及商业目的，鼓励标准使用者尝试采用不同厂家或型号的仪器。7SN/T 5324.32020附 录 B（资料性）标准物质多反应监测（MRM）色谱图图 B.1 标准物质多反应监测（MRM）色谱图沙丁胶醇15:M阳。12 Chame ES+2 2402nz1(Sabd4目31叫e5 八才00才502.00
18、 2臼3 3回4 4伺E&50 也15:M刚012Chamels ES+2 240.2 146.1(Salbul才阳17，刚eB)A 1.00 1.50 2.00 2囚3 3臼4 4切E 5.臼E 雷尼番丁57:M阳。12Cham由ES+2.17 31&2 176.1(R斟才tk0f2me6l A 1.00 1.50 2.00 2.50 3 3臼4 4.50 E 5.50 E 57:M阳。12Chamels ES+2.17 315i21301(Rm6tM弘Mee5)八1.00 1.50 2.00 2臼3 3臼4 4回E 5.50 E 扑尔敏33:M刚012Chamels ES+3.55 275
19、.096 201.161(Chlor阶町阳Bm50ee 4)八1.00 1.50 2.00 2.囚3.3.臼4 4.切E 5.囚6.33:M刚012Chamels ES+3.55 27&囚6166.骑自(CHor前町7am22neesi 才001.50 2.00 2囚3 3臼4 4囚E E囚E 24:M酬。12Chamels ES+普茶洛尔4.阔2自03183(FOF4am13beo5 八1.00 1.50 2.00 2回3 3回4 4.回E&50 E 24:M阳012Chame悟ES+4创2创I31161(FOFBam29bo5 八1.00 1.50 2.00 2臼3 3臼4 4.50 E
20、E臼6.异丙嚓42:MRM 01 2Chamels ES+265川1佣1lPromeIh4a1制zmee5i 1.00 1.50 2.00 2臼3 3臼4 4.50 E&50 E 42:M阳。12Chamels ES+282H 2881Promeh2a 122meeB)1.00 1.50 2.00 2臼3 3臼4 4.50 E 5.50 E 苯海拉明23:M刚012Chamels ES+5.22 EBh1871(DlpMWda3m25ees)八1.00 1.50 2.00 2.臼3.3.目4 4.50 E 5.囚6.23:M阳。12Chame陆ES+5.22 256.1 152(Diph酬的1
21、m94ee5i A 1.00 1.50 2.00 2回3 3团4.00 4团E 5.50 E 阿替洛尔29:MRM 012ChamelsES+2.14 267.2才创1(A148m10bel5)1.00 1.50 2.00 2.团3.3.50 4 4.切E&50 6.29:M阳012Chame ES+2.15 267.2叫45I1A158m8hbo5 Time 1.00 1.50 2.00 2臼3 3臼4 4.50 E 5.50 E 西咪替丁21 MRM 01 2 Ch.nne 5 ES+1事2:4 25111591(Clmd1M2I1neeB 1.00 1.50 2.00 2.50 3.00
22、 3.50 4.00 4.50 5.00 5.50 6.00 21 MRM of 2 Channe s ES+2:4 26311171(ClmeBtMHIneeE Time 1.00 1.50 2.00 2.50 3.00 350 4.00 4.50 500 550 600 8SN/T 5324.32020ForewordThis standard is drafted according to GB/T 1.12009、GB/T 20001.42001 和 SN/T 00012016.Please note that some of the contents of this document
23、 may involve patents.The issuing body of this document does not undertake the responsibility of identifying these patents.This standard is proposed by and is under the jurisdiction of General Administration of Customs,P.R.China.The standard is drafted by Beijing Customs District P.R.China,Beijing Ac
24、ademy of Food Science and Huangdao Customs District P.R.China，CPLA CDCP.The main drafters of this standard are Liu Ying,Liang Nana,Wang Peiyue,Han Shen,Qi Heming,Gu Jin,Cui Fengyun,Feng Xin,Guo Qinglong and Zhang Can.9SN/T 5324.32020Determination of chlorpheniramine,cimetidine,promethazine,diphenhyd
25、ramine,ranitidine,atenolol,propranolol and salbutamol in exported packaged water and drinking natural mineral water LC-MS/MS method1 ScopeThis standard specifies the determination method of cimetidine，diphenhydramine，ranitidine,salbutamol,chlorpheniramine，promethazine，atenolol and propranolol in pur
26、ified drinking water,natural drinking mineral water and other drinking water by liquid chromatography tandem mass spectrometry（LC-MS）.This standard is applicable to the determination of cimetidine，diphenhydramine，ranitidine,salbutamol,chlorpheniramine，promethazine，atenolol and propranolol in purifie
27、d drinking water,natural drinking mineral water and other drinking water.2 Normative referenceThe following document is necessary for this standard.For dated reference,only dated editions shall apply to this standard.For undated references,the latest edition of the normative document referred to app
28、ly.GB/T 33087 Ultra pure water for instrumental analysis specification and test methods.3 Terms and definitionsThere are no terms and definitions to be defined in this document.4 PrincipleThe PPCPs in samples are separated and determinated directly by LC-MS.External standard method is used to determ
29、ine the concentration of the PPCPs.5 Regents and materialsUnless otherwise specified,all the regents used should be chromatographic grade.“Water”is the ultra pure water for instrumental analysis prescribed by GB/T 33087.5.1 Formic acid.5.2 Methanol.5.3 Acetonitrile.5.4 0.5%Formic acid water solution
30、:dissolve 5 mL formic acid（5.1）in 1 000 mL water.5.5 20%Methanol water solution:dissolve 20 mL methanol（5.2）in 100 mL water.5.6 Atenolol reference standard：C14H22N2O3，CAS 29122-68-7，purity 99%。10SN/T 5324.320205.7 Propranolol reference standard：C16H21NO2.，CAS 525-66-6，purity 99%。5.8 Salbutamol refer
31、ence standard：C13H21NO3，CAS 18559-94-9，purity 99%。5.9 Chlorpheniramine reference standard：C20H23ClN2O4，CAS 113-92-8，purity 99%。5.10 Cimetidine reference standard：C10H16N6S，CAS 51481-61-9，purity 99%。5.11 Promethazine reference standard：C17H20N2S，CAS 60-87-7，purity 99%。5.12 Diphenhydramine reference s
32、tandard：C17H21NO，CAS 58-73-1，purity 99%。5.13 Ranitidine reference standard：C13H22N4O3S，CAS 66357-35-5,purity 99%。5.14 Standard stock solution:separately weigh an adequate amount of reference standards（to the nearest 0.1 mg）and dissolve in a small amount of methanol（5.2）,then fill to the volume of 10
33、 mL using methanol.The concentration of each reference standard stock solution is 1000 mg/L.5.15 Standard mix intermediate concentration solution:accurately pipette 0.1 mL of each standard stock solution（5.14）.Fill to the volume of 10 mL using methanol（5.2）.The concentration of each reference standa
34、rd is 10 mg/L in the mix intermediate concentration solution.5.16 Standard working solution:pipette adequate amount of standard mix intermediate concentration solution（5.15）,dilute with 20%Methanol water solution（5.15）to prepare appropriate concentration standard working solutions.The concentration
35、of these working solutions are 0.05 ng/mL,0.1 ng/mL,0.2 ng/mL,0.5 ng/mL,2 ng/mL,10 ng/mL,25 ng/mL,40 ng/mL.6 Apparatus and equipment6.1 High performance liquid chromatography:equipped with electric spray ion source（ESI）.6.2 Analytical balance:a sensitivity of 0.1 mg.6.3 Centrifuge:12 000 r/min.6.4 P
36、lug centrifuge tube:2 mL.6.5 Nylon millipore filter film:0.22 m.7 Procedure7.1 Sample preparationMix the waters samples and pipet 2 mL sample to the centrifuge tube（6.4）and centrifuge for 5 min at 14 000 r/min.Filter the supernatant with Nylon millipore filter film（6.5）for LC-MS analysis.7.2 Sample
37、storageThe test samples should be stored at 4.7.3 Determination7.3.1 HPLC operation conditionsHPLC conditions are as follows:a）Mobile phase（A）:Acetonitrile;mobile phase（B）:0.5%formic acid-water solution;b）Chromatographic column:C18,100 mm2.1 mm（inner diameter）,1.7 m or equivalent;c）Flow rate:0.35 mL
38、/min;d）Injection volume:5 L;e）Column temperature:40 ;11SN/T 5324.32020f）Gradient elution:according to table 1.Table 1 Liquid chromatography gradient elution procedureTime/minA/%B/%0.05.0 95.0 0.55.0 95.0 3.030.0 70.0 9.095.0 5.0 10.095.0 5.0 10.55.0 95.0 12.05.0 95.0 7.3.2 Mass spectrometry operatio
39、n conditionsMass spectrometry operation conditions are as follows:a）Ion source:ESI+;b）Determination mode:multiple reaction mode（MRM）;c）Before the detection adjust the Mass parameters to ensure the sensibility.Reference parameters according to Annex A.7.3.3 Conformation determinationThe qualification
40、 ions should be found and at least include one precursor ion and two product ions.At the same testing conditions,the variation range of the retention time for the peaks of analytes in unknown sample and in the standard solution can not be out of the range of 5%.For the same analysis batch and same c
41、ompound,the variation range of the ion ratio the two product ions for the unknown sample and the working standard solution at the similar concentration can not be out of the range of table 2.Table 2 Maximum permitted tolerance for relative ion intensities while conformationRelative intensity/（%）5020
42、 to 5010 to 20 10Permitted tolerance/（%）202530507.3.4 Quantification determinationUnder optimum working conditions,the standard working solution is selected with similar response to that of sample solution.The response of each compound in the standard working solution and sample solution should be i
43、n the linear range of the instrumental detection.The concentration of working standard solution is set as abscissa and peak area response value as ordinate,using external calibration curve for quantitative analysis.Under the 6.3 LC-MS condition,the retention time of the compounds can be referring in
44、 annex A.The MRM chromatograms are showed in annex B.7.3.5 Blank testThe operation of blank test is the same as the described in the method of determination,but with samples 12SN/T 5324.32020replaced by water.8 Calculation and expression of the result Prednisolone,Dexamethasone,Beclomethasone diprop
45、ionate and Hydrocortisone in purified drinking water,natural drinking mineral water and other drinking water are calculated using formula（1）.Calculate the content of analytes in the test sample using LC-MS data processor and the formula（1）.The blank value should be subtracted from the result of calc
46、ulation:Xi=cif（1）Where:Xi the residue content of PPCPs,ng/mL;ci the concentration of testing sample solution gained by data processor,ng/mL;f sample dilution ratio.The results are rounded off to three significant figures.9 Limit of quantification and recovery9.1 Limit of quantificationThe limit of q
47、uantification for chlorpheniramine,cimetidine,promethazine,diphenhydramine,ranitidine,atenolol,propranolol and salbutamol in purified drinking water,natural drinking mineral water and other drinking water are 0.5 ng/mL.9.2 RecoveryThe recovery data in different spiked levels of chlorpheniramine,cime
48、tidine,promethazine,diphenhydramine,ranitidine,atenolol,propranolol and salbutamol in purified drinking water,natural drinking mineral water and other drinking water are listed in table 3.Table 3 The spiked levels and recovery ranges of chlorpheniramine,cimetidine,promethazine,diphenhydramine,raniti
49、dine,atenolol,propranolol and salbutamol in purified drinking water,natural drinking mineral water and other drinking water（n=6）CompoundSpiked level/（ng/mL）Recovery range（%）Purified drinking waterOther drinking waterNatural drinking mineral waterAtenolol0.0589.8-96.785.2-91.793.7-106.90.194.5-105.78
50、4.0-103.296.7-107.60.593.1-105.686.3-93.789.2-95.7Propanolol 0.0588.0-101.882.0-93.384.4-90.40.187.0-92.785.5-108.983.2-91.10.592.0-96.4104.8-107.395.3-107.113SN/T 5324.32020Table 3（续）CompoundSpiked level/（ng/mL）Recovery range（%）Purified drinking waterOther drinking waterNatural drinking mineral wat