CN113759051A - 一种测量碘化钠口服溶液中edta含量的检测方法 - Google Patents
一种测量碘化钠口服溶液中edta含量的检测方法 Download PDFInfo
- Publication number
- CN113759051A CN113759051A CN202111128494.8A CN202111128494A CN113759051A CN 113759051 A CN113759051 A CN 113759051A CN 202111128494 A CN202111128494 A CN 202111128494A CN 113759051 A CN113759051 A CN 113759051A
- Authority
- CN
- China
- Prior art keywords
- solution
- edta
- measuring
- sample
- detection method
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 title claims abstract description 30
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 238000001514 detection method Methods 0.000 title claims abstract description 20
- 229940100688 oral solution Drugs 0.000 title claims abstract description 13
- 235000009518 sodium iodide Nutrition 0.000 title claims abstract description 10
- 239000000523 sample Substances 0.000 claims abstract description 31
- 239000007788 liquid Substances 0.000 claims abstract description 19
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 16
- 239000011630 iodine Substances 0.000 claims abstract description 16
- 238000007865 diluting Methods 0.000 claims abstract description 8
- 238000001914 filtration Methods 0.000 claims abstract description 6
- 239000012488 sample solution Substances 0.000 claims abstract description 6
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims abstract description 5
- 101710134784 Agnoprotein Proteins 0.000 claims abstract description 3
- 239000012528 membrane Substances 0.000 claims abstract description 3
- 229910052979 sodium sulfide Inorganic materials 0.000 claims abstract 2
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 claims abstract 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 claims description 8
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 7
- 238000004587 chromatography analysis Methods 0.000 claims description 3
- 238000010829 isocratic elution Methods 0.000 claims description 3
- 235000017281 sodium acetate Nutrition 0.000 claims description 3
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 239000011148 porous material Substances 0.000 claims description 2
- 229940087562 sodium acetate trihydrate Drugs 0.000 claims description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 abstract description 26
- 229910001961 silver nitrate Inorganic materials 0.000 abstract description 13
- 230000002285 radioactive effect Effects 0.000 abstract description 12
- 238000000034 method Methods 0.000 abstract description 9
- 239000000047 product Substances 0.000 abstract description 9
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 abstract description 7
- 150000002500 ions Chemical class 0.000 abstract description 6
- 238000004458 analytical method Methods 0.000 abstract description 4
- 229910000406 trisodium phosphate Inorganic materials 0.000 abstract description 4
- 239000000463 material Substances 0.000 abstract description 3
- JKFYKCYQEWQPTM-UHFFFAOYSA-N 2-azaniumyl-2-(4-fluorophenyl)acetate Chemical compound OC(=O)C(N)C1=CC=C(F)C=C1 JKFYKCYQEWQPTM-UHFFFAOYSA-N 0.000 abstract description 2
- 229910021612 Silver iodide Inorganic materials 0.000 abstract description 2
- OCVXZQOKBHXGRU-UHFFFAOYSA-N iodine(1+) Chemical compound [I+] OCVXZQOKBHXGRU-UHFFFAOYSA-N 0.000 abstract description 2
- 239000002244 precipitate Substances 0.000 abstract description 2
- 230000008569 process Effects 0.000 abstract description 2
- 229940045105 silver iodide Drugs 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 16
- 239000012071 phase Substances 0.000 description 15
- 239000008227 sterile water for injection Substances 0.000 description 13
- 238000012360 testing method Methods 0.000 description 12
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 10
- 239000000203 mixture Substances 0.000 description 8
- 238000000926 separation method Methods 0.000 description 8
- 239000012085 test solution Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 238000001228 spectrum Methods 0.000 description 7
- 238000005303 weighing Methods 0.000 description 7
- 239000012490 blank solution Substances 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- JLKDVMWYMMLWTI-UHFFFAOYSA-M potassium iodate Chemical compound [K+].[O-]I(=O)=O JLKDVMWYMMLWTI-UHFFFAOYSA-M 0.000 description 4
- 239000001230 potassium iodate Substances 0.000 description 4
- 235000006666 potassium iodate Nutrition 0.000 description 4
- 229940093930 potassium iodate Drugs 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- 238000004448 titration Methods 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 238000010668 complexation reaction Methods 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 3
- 238000012795 verification Methods 0.000 description 3
- VTLYFUHAOXGGBS-UHFFFAOYSA-N Fe3+ Chemical compound [Fe+3] VTLYFUHAOXGGBS-UHFFFAOYSA-N 0.000 description 2
- LFVGISIMTYGQHF-UHFFFAOYSA-N ammonium dihydrogen phosphate Chemical compound [NH4+].OP(O)([O-])=O LFVGISIMTYGQHF-UHFFFAOYSA-N 0.000 description 2
- 229910000387 ammonium dihydrogen phosphate Inorganic materials 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 235000019837 monoammonium phosphate Nutrition 0.000 description 2
- 239000013074 reference sample Substances 0.000 description 2
- 239000012088 reference solution Substances 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 229910000162 sodium phosphate Inorganic materials 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 229910000153 copper(II) phosphate Inorganic materials 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000013101 initial test Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000004189 ion pair high performance liquid chromatography Methods 0.000 description 1
- 150000008040 ionic compounds Chemical class 0.000 description 1
- WBJZTOZJJYAKHQ-UHFFFAOYSA-K iron(3+) phosphate Chemical compound [Fe+3].[O-]P([O-])([O-])=O WBJZTOZJJYAKHQ-UHFFFAOYSA-K 0.000 description 1
- 229910000399 iron(III) phosphate Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 235000013324 preserved food Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 239000012217 radiopharmaceutical Substances 0.000 description 1
- 229940121896 radiopharmaceutical Drugs 0.000 description 1
- 230000002799 radiopharmaceutical effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- MKWYFZFMAMBPQK-UHFFFAOYSA-J sodium feredetate Chemical compound [Na+].[Fe+3].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O MKWYFZFMAMBPQK-UHFFFAOYSA-J 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 235000013555 soy sauce Nutrition 0.000 description 1
- 239000012086 standard solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
Abstract
本发明提供一种测量碘化钠口服溶液中EDTA含量的检测方法,包括以下步骤:S1:取待测的碘[131I]化钠样品溶液0.1ml,向其中加入0.1ml 2%AgNO3溶液,0.05ml 1%FeCl3溶液,稀释定容至5ml,用滤膜过滤即得待测液;S2:采用高效液相色谱仪自动进样、检测;本分析方法在样品的前处理过程中加入硝酸银使放射性碘[131I]离子和非放射性的碘同位素以碘化银形式沉淀下来,有效防止了放射性单质碘(131I2)的挥发。同时,产品中的其余辅料Na2SO3、Na3PO4,也会与硝酸银生产沉淀,通过过滤可除去,降低干扰。
Description
技术领域
本发明属于检测技术领域,具体涉及一种测量碘化钠口服溶液中EDTA含量的检测方法。
背景技术
目前,测定不同介质中的EDTA的方法有比色法、滴定法和高效液相色谱法。但滴定法和络合法很难将EDTA络合物和其他络合物区分,检测方法的专属性差,导致测定的数据结果不准确。高效液相色谱法一般通过检测EDTA的金属络合物EDTA-Cu和EDTA-Fe对EDTA进行测定。本公司样品中含有KI、Na2SO3、Na3PO4会与Fe3+及Cu2+发生反应,反应方程式分别如下:
2Fe3++2I-=2Fe2++I2
2Cu2++4I-=2CuI↓+I2
3CuSO4+2Na3PO4=Cu3(PO4)2↓+3Na2SO4
Na3PO4+FeCl3===FePO4↓+3NaCl
综合考虑,EDTA-Fe(Ⅲ)的稳定性强于EDTA-Cu(Ⅱ),且产品中可能含有微量的Fe3 +,因此为保证测量数据准确,选择以Fe3+作为络合剂。
经调查,EDTA-Fe(Ⅲ)络合物在酸性条件下较稳定,因此高效液相色谱法测量EDTA含量的文献中,采用的流动相pH值大多在2-4左右。但我公司产品为放射性的碘[131I]化钠口服溶液,产品的有效成分碘[131I]离子在碱性条件下最稳定,但为了保证药品稳定性的同时又能兼顾患者服用的安全性,碘[131I]化钠口服溶液的质量标准中规定的pH值范围是7.0~9.0。放射性碘[131I]离子在酸性条件下极不稳定,且又有Fe3+存在,极易产生放射性单质碘(131I2)并挥发,扩散的放射性气体给检测人员带来安全隐患,而且挥发性的单质碘(131I2)气体很容易污染仪器设备和造成研究场所的沾污。
要解决的问题:(1)提高检测方法的专属性、准确性、灵敏度,将其它辅料或杂质对分析方法的干扰降到最低;(2)防止因放射性单质碘(131I2)挥发而对检测人员造成辐照伤害,污染仪器设备或造成研究场所沾污。
发明内容
本发明的目的在于提供一种测量碘化钠口服溶液中EDTA含量的检测方法,包括以下步骤:
S1:取待测的碘[131I]化钠样品溶液0.1ml,共四组,分别向其中加入0.1ml2%AgNO3溶液,0.05ml 1%FeCl3溶液,稀释定容至5ml,用0.22μm滤膜过滤即得待测液;
S3:采用高效液相色谱仪自动进样、检测;
流动相:取四丁基硫酸氢铵6.791g,乙酸钠-三水4.082g加水1000ml溶解,同时加入磷酸调将pH值调至3.0;
色谱柱:C18色谱柱;
检测波长:254nm;
流速:1.0ml/min;
柱温:35℃;
进样量:20μl;
记录时间要求:20min等度洗脱。
作为本发明的进一步方案,在S1中,所述滤膜的孔径为0.22μm。
作为本发明的进一步方案,所述高效液相色谱仪型号为Ultimate 3000。
作为本发明的进一步方案,在S2中,所述C18色谱柱采用Agilent C18柱。
作为本发明的进一步方案,在S2中,将pH值调至3.0是通过加入磷酸。
与现有技术相比,本发明的有益效果是:
(1)采用高效液相色谱法测量碘[131I]化钠口服溶液中的EDTA含量,此方法的专属性强、准确度高、灵敏度高。
(2)本分析方法在样品的前处理过程中加入硝酸银使放射性碘[131I]离子和非放射性的碘同位素以碘化银形式沉淀下来,有效防止了放射性单质碘(131I2)的挥发。同时,产品中的其余辅料Na2SO3、Na3PO4,也会与硝酸银生产沉淀,通过过滤可除去,降低干扰。另外,样品经过前处理后,在高效液相色谱仪进样的供试品溶液残留的放射性活度很低,有效地杜绝了放射性气体扩散给检测人员带来安全隐患,同时也降低了仪器设备污染和造成研究场所沾污的风险。
(3)与普通的滴定法和络合法相比,本产品采用高效液相色谱仪自动进样、检测,同时采用铅屏风对设备进行有效的屏蔽,减少检测人员对放射性样品的接触时间,有效地降低了检测人员受放射性照射的剂量,工作人员的身体健康得到保障。
(4)放射性药品的原料来之不易且价格昂贵,若采用普通的滴定法和络合法检测EDTA含量,所需样品量多,而高效液相色谱仪属于精密仪器,进样量在20微升左右,所需的碘[131I]化钠口服溶液样品量较少,为公司节省了很大的经济成本。
附图说明
图1是EDTA-Fe(Ⅲ)光谱扫描曲线;
图2是供试品溶液高效液相色谱图;
图3是对照品溶液高效液相色谱图;
图4是空白溶液高效液相色谱图;
图5是5%乙腈下供试品高效液相色谱图;
图6是10%乙腈下供试品高效液相色谱图;
图7是15%乙腈下供试品高效液相色谱图;
图8是5%甲醇下供试品高效液相色谱图
图9是10%甲醇下供试品高效液相色谱图
图10是15%甲醇下供试品高效液相色谱图
图11是供试品溶液高效液相色谱图;
图12是对照品溶液高效液相色谱图;
图13是空白溶液高效液相色谱图。
具体实施方式
1.1.溶液配制
(1)0.5mg/mlEDTA溶液(自制标准品):称取EDTA0.050g(实际称量0.0500g)置100ml的容量瓶中,加水溶解,稀释定容至刻度,摇匀。
(2)20mg/ml硝酸银溶液:称取2.000g(实际称量:1.9998g)硝酸银于100ml容量瓶,加灭菌注射用水溶解,并定容至刻度,摇匀。放入棕色试剂瓶中保存。
(3)10mg/ml三氯化铁溶液溶液:称取1.000g(实际称量:1.0003g)三氯化铁于100ml容量瓶,加灭菌注射用水溶解,并定容至刻度,摇匀。
(4)100μg/ml的碘化钾溶液:称取碘化钾0.010g(实际称量:0.0102g)于100ml容量瓶中,加入灭菌注射用水溶解并定容至刻度,摇匀。
(5)100μg/ml的碘酸钾溶液:称取碘酸钾0.010g(实际称量:0.0101g)于100ml容量瓶中,加入灭菌注射用水溶解并定容至刻度,摇匀。
(6)无EDTA模拟供试品溶液:称取0.600g亚硫酸钠(实际称量0.6001g),5.000g磷酸钠(实际称量5.0003g)于100ml容量瓶中,再准确移取加入100μg/ml的碘化钾溶液,100μg/ml的碘酸钾溶液各1ml,用灭菌注射用水稀释定容至刻度,摇匀。
(7)模拟供试品溶液:称取2.000gEDTA(实际称量2.0001g),0.600g亚硫酸钠(实际称量0.6000g),5.000g磷酸钠(实际称量5.0003g)于100ml容量瓶中,再准确移取加入100μg/ml的碘化钾溶液,100μg/ml的碘酸钾溶液各1ml,用灭菌注射用水稀释定容至刻度,摇匀。
(8)流动相的配制:流动相A:称取15.000g磷酸二氢铵(实际称量:14.9997g)加水3000ml溶解(pH约4.54),磷酸调pH3.0。流动相B:乙腈。
1.2.初步测试
参考文献中国科技期刊数据库中的文献《依地酸二钠含量测定方法学研究》建立了以下条件。并在该条件下进行了初步测试。
流动相A:取磷酸二氢铵15g,加水3000ml溶解(pH约4.54),磷酸调pH3.0流动相B:乙腈洗脱方式:
梯度洗脱流速:1.0ml/min
进样量:20μl
柱温:35℃
1.2.1操作方式
1.对照品溶液:准确移取0.5mg/mlEDTA溶液(自制标准品)0.4ml于5ml容量瓶中,先加入20mg/ml的硝酸银溶液0.1ml,再加入10mg/ml的三氯化铁溶液0.05ml,用灭菌注射用水定容至5ml,摇匀。用0.22μm滤膜过滤,取滤液1ml于样品瓶中。
2.供试品溶液:准确移取模拟供试品溶液0.1ml于5ml容量瓶中,先加入20mg/ml的硝酸银溶液0.1ml,再加入10mg/ml的三氯化铁溶液0.05ml,用灭菌注射用水定容至5ml,摇匀。用0.22μm滤膜过滤,取滤液1ml于样品瓶中。
3.空白溶液:准确移取无EDTA模拟供试品溶液0.1ml于5ml容量瓶中,先加入20mg/ml的硝酸银溶液0.1ml,再加入10mg/ml的三氯化铁溶液0.05ml,用灭菌注射用水定容至5ml,摇匀。用0.22μm滤膜过滤,取滤液1ml于样品瓶中。
按照1.2中所示的条件进行流动相的配制以及高效液相色谱柱上的各项程序设置,并进样。
1.2.2实验结论
在该初试条件下,供试品谱图呈现为多个峰,且分离度差,拖尾严重,较难区分络合物EDTA-Fe(Ⅲ)的峰与干扰峰。且在梯度洗脱的情况下,有基线塌陷的情况。供试品溶液谱图见图2,对照品溶液谱图见图3,空白溶液见图4。
1.3.流动相的选择
实验证明在初步测试的条件下实验结果分离度差,较难通过其他条件改变分离度,因此本次实验拟通过对流动相进行调整,增大分离度。同时实验也发现梯度洗脱导致基线不平稳,因此将洗脱方式改变为等度洗脱。
1.3.1增大有机相比例
1.3.1.1乙腈
(1)操作方式:
色谱条件
操作信息表
(2)实验结论:
随着乙腈浓度的增大,谱图中所出现的两个峰之间,分离度逐渐减小,谱图如下。原始数据谱图见附图5-7。
1.3.1.2甲醇
上述实验结果表明,在乙腈浓度逐渐加大的情况下,待测物与干扰物的分离度没有改善。根据文献查阅,甲醇的加入有利于离子类化合物的分离,因此考虑使用甲醇作为有机相进行测试。
(1)操作方式
色谱条件
操作方式
(2)实验结果:
随着甲醇浓度的增大,谱图中所出现的两个峰之间,分离度逐渐减小,且峰型变差。谱图参考8-10。
1.3.2离子对试剂
经实验验证与理论分析,证明有机相的加入对本产品中EDTA-Fe(Ⅲ)络合物与其他干扰因素的分离没有帮助作用,且随着有机相的加入,各峰的保留时间提前,并逐渐重合,不利于测量。因此考虑改变离子对试剂,同时采用纯水相作为流动相,增大EDTA-Fe(Ⅲ)络合物的保留时间,从而增大分离度。
目前酸性条件下,常用的离子对试剂有四丁基溴化铵、四丁基硫酸氢铵等,结合文献与实际,筛选了如下的流动相条件:四丁基硫酸氢铵(0.02mol/L)乙酸钠(0.03mol/L),磷酸调pH为3作为初试条件。参考文献《反相高效液相色谱法测定罐头食品中乙二胺四乙酸的残留量》,《反相离子对高效液相色谱法测定铁强化酱油中的乙二胺四乙酸铁钠》。
1.3.2.1操作方式
色谱条件
1.对照品溶液:准确移取0.5mg/mlEDTA溶液(自制标准品)0.4ml于5ml容量瓶中,先加入20mg/ml的硝酸银溶液0.1ml,再加入10mg/ml的三氯化铁溶液0.05ml,用灭菌注射用水定容至5ml,摇匀。用0.22μm滤膜过滤,取滤液1ml于样品瓶中。
2.供试品溶液:准确移取模拟供试品溶液0.1ml于5ml容量瓶中,先加入20mg/ml的硝酸银溶液0.1ml,再加入10mg/ml的三氯化铁溶液0.05ml,用灭菌注射用水定容至5ml,摇匀。用0.22μm滤膜过滤,取滤液1ml于样品瓶中。
3.空白溶液:准确移取无EDTA模拟供试品溶液0.10.1ml于5ml容量瓶中,先加入20mg/ml的硝酸银溶液0.1ml,再加入10mg/ml的三氯化铁溶液0.05ml,用灭菌注射用水定容至5ml,摇匀。用0.22μm滤膜过滤,取滤液1ml于样品瓶中。
按照表上所示的方式配制流动相以及在仪器上设置相应参数,进行进样及测试。
1.3.1.2实验结论
在该实验条件下,色谱图上供试品出峰情况与对照品峰出峰时间一致,峰型一致,空白溶液在供试品与对照品出峰位置无干扰。谱图如下。原始数据谱图见附图11-13。
2.实验条件线性验证
2.1.操作方法:
表12:色谱条件
取5个5ml的容量瓶,分别加入0.5mg/ml的EDTA溶液(自制标准品溶液)0.0ml、0.1ml、0.2ml、0.3ml、0.4ml、0.5ml,每个容量瓶再各先加入20mg/ml硝酸银溶液0.1ml及10mg/ml三氯化铁溶液0.05ml,用灭菌注射用水定容至5ml,摇匀。最后,分别用0.22μm滤膜过滤,并取1ml滤液于样品瓶中按表12的HPLC参数,测试条件进样,使用UV检测器记录色谱图。
2.2.实验结果
3.实验确立测量方案
因EDTA含量并不在产品质量标准中,本方案的建立是为了从EDTA的含量变化情况判断其是否发生了辐照降解。因此只需要对EDTA含量进行基本测量,精度要求不高。因此经上述实验,最终以表4-1所示的实验条件进行测量,该测量条件可实现对于产品中EDTA含量的简单测量,可进行下一步的方法学验证。
实验最终测量条件
本具体实施例仅仅是对本发明的解释,其并不是对本发明的限制,本领域技术人员在阅读完本说明书后可以根据需要对本实施例做出没有创造性贡献的修改,但只要在本发明的权利要求范围内都受到专利法的保护。。
Claims (5)
1.一种测量碘化钠口服溶液中EDTA含量的检测方法,其特征在于,包括以下步骤:
S1:取待测的碘[131I]化钠样品溶液0.1ml,向其中加入0.1ml 2%AgNO3溶液,0.05ml1%FeCl3溶液,稀释定容至5ml,用滤膜过滤即得待测液;
S2:采用高效液相色谱仪自动进样、检测;
流动相:取四丁基硫酸氢铵6.791g,乙酸钠-三水4.082g加水1000ml溶解,同时加入磷酸调将pH值调至3.0;
色谱柱:C18色谱柱;
检测波长:254nm;
流速:1.0ml/min;
柱温:35℃;
进样量:20μl;
记录时间要求:20min等度洗脱。
2.根据权利要求1所述的测量碘化钠口服溶液中EDTA含量的检测方法,其特征在于:在S1中,所述滤膜的孔径为0.22μm。
3.根据权利要求1所述的测量碘化钠口服溶液中EDTA含量的检测方法,其特征在于:所述高效液相色谱仪型号为Ultimate 3000。
4.根据权利要求1所述的测量碘化钠口服溶液中EDTA含量的检测方法,其特征在于:在S2中,所述C18色谱柱采用Agilent C18柱。
5.根据权利要求1所述的测量碘化钠口服溶液中EDTA含量的检测方法,其特征在于:在S2中,将pH值调至3.0是通过加入磷酸。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111128494.8A CN113759051A (zh) | 2021-09-26 | 2021-09-26 | 一种测量碘化钠口服溶液中edta含量的检测方法 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202111128494.8A CN113759051A (zh) | 2021-09-26 | 2021-09-26 | 一种测量碘化钠口服溶液中edta含量的检测方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN113759051A true CN113759051A (zh) | 2021-12-07 |
Family
ID=78797453
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202111128494.8A Pending CN113759051A (zh) | 2021-09-26 | 2021-09-26 | 一种测量碘化钠口服溶液中edta含量的检测方法 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN113759051A (zh) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114755342A (zh) * | 2022-04-25 | 2022-07-15 | 湖北科伦药业有限公司 | 一种硫酸庆大霉素注射液中辅料edta的检测方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102798678A (zh) * | 2012-08-31 | 2012-11-28 | 成都百裕科技制药有限公司 | 注射用泮托拉唑钠中依地酸钙钠的检测及含量测定方法 |
CN110794045A (zh) * | 2018-08-03 | 2020-02-14 | 上海聚可医药科技有限公司 | 一种乙酰半胱氨酸液体制剂中依地酸二钠的含量测定方法 |
CN111948299A (zh) * | 2019-05-15 | 2020-11-17 | 上海现代药物制剂工程研究中心有限公司 | 测定泊沙康唑注射液中乙二胺四乙酸二钠含量的方法 |
CN111983072A (zh) * | 2020-08-14 | 2020-11-24 | 扬州中宝药业股份有限公司 | 一种乙酰半胱氨酸雾化吸入溶液所含乙二胺四醋酸二钠的检测方法 |
-
2021
- 2021-09-26 CN CN202111128494.8A patent/CN113759051A/zh active Pending
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102798678A (zh) * | 2012-08-31 | 2012-11-28 | 成都百裕科技制药有限公司 | 注射用泮托拉唑钠中依地酸钙钠的检测及含量测定方法 |
CN110794045A (zh) * | 2018-08-03 | 2020-02-14 | 上海聚可医药科技有限公司 | 一种乙酰半胱氨酸液体制剂中依地酸二钠的含量测定方法 |
CN111948299A (zh) * | 2019-05-15 | 2020-11-17 | 上海现代药物制剂工程研究中心有限公司 | 测定泊沙康唑注射液中乙二胺四乙酸二钠含量的方法 |
CN111983072A (zh) * | 2020-08-14 | 2020-11-24 | 扬州中宝药业股份有限公司 | 一种乙酰半胱氨酸雾化吸入溶液所含乙二胺四醋酸二钠的检测方法 |
Non-Patent Citations (5)
Title |
---|
JAMES E. ANDERSON ET AL: "Incomplete Oxidation of Ethylenediaminetetraacetic Acid in Chemical Oxygen Demand Analysis" * |
关炳峰 等: "高效液相色谱法测定小麦粉中乙二胺四乙酸二钠的方法优化" * |
施旭霞 等: "反相高效液相色谱法测定罐头食品中乙二胺四乙酸的残留量" * |
王玲钰 等: "放射性尾气中碘的净化处理研究进展" * |
魏峰 等: "反相离子对高效液相色谱法测定铁强化酱油中的乙二胺四乙酸铁钠" * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114755342A (zh) * | 2022-04-25 | 2022-07-15 | 湖北科伦药业有限公司 | 一种硫酸庆大霉素注射液中辅料edta的检测方法 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Fifield | Principles and practice of analytical chemistry | |
Aydin et al. | Solid phase extraction and preconcentration of uranium (VI) and thorium (IV) on Duolite XAD761 prior to their inductively coupled plasma mass spectrometric determination | |
Hu et al. | Simultaneous determination of palladium, platinum, rhodium and gold by on-line solid phase extraction and high performance liquid chromatography with 5-(2-hydroxy-5-nitrophenylazo) thiorhodanine as pre-column derivatization regents | |
Coedo et al. | Isotope dilution analysis for flow injection ICPMS determination of microgram per gram levels of boron in iron and steel after matrix removal | |
CN113759051A (zh) | 一种测量碘化钠口服溶液中edta含量的检测方法 | |
Sabermahani et al. | Separation and preconcentration of trace amounts of gold from water samples prior to determination by flame atomic absorption spectrometry | |
CN106556649B (zh) | 丁酸氯维地平注射乳剂中依地酸二钠的检测方法 | |
Cao et al. | Elimination of the spectral interference from polyatomic ions with rare earth elements in inductively coupled plasma mass spectrometry by combining algebraic correction with chromatographic separation | |
CN104215627A (zh) | 微波消解-icp-ms测定烟盒中的金属离子铅、砷、镉和铬的方法 | |
Lerner et al. | A chemically modified silica-gel as an ion exchange resin for pre-concentration of actinides and lanthanides | |
Zhou et al. | Simultaneous total and speciation analysis of rhenium by capillary electrophoresis-inductively coupled plasma mass spectrometry | |
Ferri et al. | Differential pulse polarographic determination of arsenic, selenium and tellurium at μg levels | |
Sterritt et al. | Comparison of methods for the determination of conditional stability constants of heavy metal-fulvic acid complexes | |
Anderson et al. | Coatings | |
CN111189956B (zh) | H2o2氧化离子色谱检测氯化钠样品中亚硝酸盐含量的方法 | |
Wu et al. | Speciation of vanadium in water with quinine modified resin micro-column separation/preconcentration and their determination by fluorination assisted electrothermal vaporization (FETV)–inductively coupled plasma optical emission spectrometry (ICP-OES) | |
Jaison et al. | Electrospray ionisation mass spectrometric studies for the determination of palladium after pre‐concentration by disposable pipette extraction | |
Pourreza et al. | Solid phase preconcentration of iron as methylthymol blue complex on naphthalene-tetraoctylammonium bromide adsorbent with subsequent flame atomic absorption determination | |
CN113325118B (zh) | 一种测定帕瑞昔布钠中钠含量的方法 | |
CN103175930B (zh) | 一种测定亚硫酸钠含量的高效液相色谱分析方法 | |
Rezaei et al. | Preconcentration of thallium (III) with 2, 6-bis (N-phenyl carbamoyl) pyridine on microcrystalline naphthalene prior to its trace determination in human serum spectrophotometrically | |
Sutton et al. | High-performance chelation ion chromatography for the determination of traces of bismuth in lead by means of a novel hypercrosslinked polystyrene resin | |
Shamspur | Solid phase extraction of trace amounts of palladium ions using multiwalled carbon nanotube modified by N, N’-bis (2-hydroxy-benzylidene)-2, 2’(aminophenylthio) ethane prior to determination by flame atomic absorption spectrometry | |
Hasani et al. | H-point standard addition method for simultaneous determination of Fe (II), Co (II) and Cu (II) in micellar media with simultaneous addition of three analytes | |
Fardy et al. | Rapid radiochemical separation in neutron activation analysis: Part 1. The use of C18-bonded silica gel and selective complexation for determinations of manganese, copper and zinc in biological materials |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20211207 |