CN113686980A - Method for simultaneously determining content of 24 element impurities in hydroxyethyl starch sodium chloride injection - Google Patents
Method for simultaneously determining content of 24 element impurities in hydroxyethyl starch sodium chloride injection Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 30
- 229920001612 Hydroxyethyl starch Polymers 0.000 title claims abstract description 29
- 229940050526 hydroxyethylstarch Drugs 0.000 title claims abstract description 29
- 239000012535 impurity Substances 0.000 title claims abstract description 29
- 239000008354 sodium chloride injection Substances 0.000 title claims abstract description 23
- 239000002904 solvent Substances 0.000 claims abstract description 25
- 239000012086 standard solution Substances 0.000 claims abstract description 17
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000009616 inductively coupled plasma Methods 0.000 claims abstract description 11
- 239000012488 sample solution Substances 0.000 claims abstract description 9
- 239000000523 sample Substances 0.000 claims abstract description 6
- 239000007789 gas Substances 0.000 claims description 21
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 claims description 19
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 19
- 239000010931 gold Substances 0.000 claims description 14
- 239000010948 rhodium Substances 0.000 claims description 14
- 238000007865 diluting Methods 0.000 claims description 13
- 239000012159 carrier gas Substances 0.000 claims description 10
- 239000011651 chromium Substances 0.000 claims description 10
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 claims description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
- 239000011669 selenium Substances 0.000 claims description 8
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 6
- 229910052793 cadmium Inorganic materials 0.000 claims description 6
- BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 claims description 6
- 229910052802 copper Inorganic materials 0.000 claims description 6
- 239000010949 copper Substances 0.000 claims description 6
- 229910017604 nitric acid Inorganic materials 0.000 claims description 6
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 claims description 5
- ZOKXTWBITQBERF-UHFFFAOYSA-N Molybdenum Chemical compound [Mo] ZOKXTWBITQBERF-UHFFFAOYSA-N 0.000 claims description 5
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 5
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 5
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 claims description 5
- 229910052785 arsenic Inorganic materials 0.000 claims description 5
- RQNWIZPPADIBDY-UHFFFAOYSA-N arsenic atom Chemical compound [As] RQNWIZPPADIBDY-UHFFFAOYSA-N 0.000 claims description 5
- 229910052788 barium Inorganic materials 0.000 claims description 5
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 claims description 5
- 229910017052 cobalt Inorganic materials 0.000 claims description 5
- 239000010941 cobalt Substances 0.000 claims description 5
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 claims description 5
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 5
- 229910052737 gold Inorganic materials 0.000 claims description 5
- 239000001307 helium Substances 0.000 claims description 5
- 229910052734 helium Inorganic materials 0.000 claims description 5
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 claims description 5
- 229910052741 iridium Inorganic materials 0.000 claims description 5
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 5
- 238000001819 mass spectrum Methods 0.000 claims description 5
- 229910052753 mercury Inorganic materials 0.000 claims description 5
- 229910052759 nickel Inorganic materials 0.000 claims description 5
- 229910052697 platinum Inorganic materials 0.000 claims description 5
- 229910052703 rhodium Inorganic materials 0.000 claims description 5
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 5
- 229910052707 ruthenium Inorganic materials 0.000 claims description 5
- 229910052711 selenium Inorganic materials 0.000 claims description 5
- 229910052716 thallium Inorganic materials 0.000 claims description 5
- BKVIYDNLLOSFOA-UHFFFAOYSA-N thallium Chemical compound [Tl] BKVIYDNLLOSFOA-UHFFFAOYSA-N 0.000 claims description 5
- 229910052718 tin Inorganic materials 0.000 claims description 5
- 229910052720 vanadium Inorganic materials 0.000 claims description 5
- LEONUFNNVUYDNQ-UHFFFAOYSA-N vanadium atom Chemical compound [V] LEONUFNNVUYDNQ-UHFFFAOYSA-N 0.000 claims description 5
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 claims description 4
- 229910052804 chromium Inorganic materials 0.000 claims description 4
- 229910052762 osmium Inorganic materials 0.000 claims description 4
- SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 claims description 4
- 229910052709 silver Inorganic materials 0.000 claims description 4
- 239000004332 silver Substances 0.000 claims description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
- 229910052771 Terbium Inorganic materials 0.000 claims description 3
- 229910052787 antimony Inorganic materials 0.000 claims description 3
- WATWJIUSRGPENY-UHFFFAOYSA-N antimony atom Chemical compound [Sb] WATWJIUSRGPENY-UHFFFAOYSA-N 0.000 claims description 3
- 229910052797 bismuth Inorganic materials 0.000 claims description 3
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 claims description 3
- 238000012937 correction Methods 0.000 claims description 3
- 229910052732 germanium Inorganic materials 0.000 claims description 3
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 claims description 3
- 229910052738 indium Inorganic materials 0.000 claims description 3
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 claims description 3
- 229910052744 lithium Inorganic materials 0.000 claims description 3
- 229910052750 molybdenum Inorganic materials 0.000 claims description 3
- 239000011733 molybdenum Substances 0.000 claims description 3
- 229910052763 palladium Inorganic materials 0.000 claims description 3
- 230000002572 peristaltic effect Effects 0.000 claims description 3
- 238000005070 sampling Methods 0.000 claims description 3
- 229910052706 scandium Inorganic materials 0.000 claims description 3
- SIXSYDAISGFNSX-UHFFFAOYSA-N scandium atom Chemical compound [Sc] SIXSYDAISGFNSX-UHFFFAOYSA-N 0.000 claims description 3
- 239000000243 solution Substances 0.000 claims description 3
- GZCRRIHWUXGPOV-UHFFFAOYSA-N terbium atom Chemical compound [Tb] GZCRRIHWUXGPOV-UHFFFAOYSA-N 0.000 claims description 3
- 238000012360 testing method Methods 0.000 claims description 3
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 3
- 239000012498 ultrapure water Substances 0.000 claims description 3
- 229910052727 yttrium Inorganic materials 0.000 claims description 3
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 claims description 3
- 239000000956 alloy Substances 0.000 claims 1
- 238000001514 detection method Methods 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 4
- 206010070834 Sensitisation Diseases 0.000 abstract description 3
- 239000003085 diluting agent Substances 0.000 abstract description 3
- 238000003672 processing method Methods 0.000 abstract description 3
- 230000008313 sensitization Effects 0.000 abstract description 3
- 239000012088 reference solution Substances 0.000 abstract description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 230000035939 shock Effects 0.000 description 3
- HBBGRARXTFLTSG-UHFFFAOYSA-N Lithium ion Chemical compound [Li+] HBBGRARXTFLTSG-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- FAWGZAFXDJGWBB-UHFFFAOYSA-N antimony(3+) Chemical compound [Sb+3] FAWGZAFXDJGWBB-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 229920000945 Amylopectin Polymers 0.000 description 1
- 208000007204 Brain death Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 208000029028 brain injury Diseases 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
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- 230000000593 degrading effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000003394 haemopoietic effect Effects 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
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- 230000004089 microcirculation Effects 0.000 description 1
- 230000009251 neurologic dysfunction Effects 0.000 description 1
- 208000015015 neurological dysfunction Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
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- 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
-
- 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
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- 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
- G01N30/72—Mass spectrometers
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- 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
- G01N30/86—Signal analysis
- G01N30/8675—Evaluation, i.e. decoding of the signal into analytical information
- G01N30/8679—Target compound analysis, i.e. whereby a limited number of peaks is analysed
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- 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
- G01N2030/042—Standards
- G01N2030/045—Standards internal
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Abstract
The invention relates to a method for simultaneously determining the content of 24 element impurities in hydroxyethyl starch sodium chloride injection, which comprises the following steps: preparing a reference solution, preparing an internal standard solution, preparing a sample solution, injecting the sample solution into an inductively coupled plasma mass spectrometer, and detecting by adopting an internal standard calibration standard curve method, so that the content of 24 element impurities in the hydroxyethyl starch sodium chloride injection can be simultaneously measured; the method for simultaneously determining the content of the impurities of the 24 elements in the hydroxyethyl starch sodium chloride injection improves the stability of low-concentration Hg by optimizing a sample processing method and using a first solvent as a diluent and a standard solution to prepare the solvent, reduces the sensitization effect of organic matters by adding a proper amount of isopropanol into an internal standard solution, overcomes the interference of the organic matters, optimizes instrument parameters, formulates the method capable of simultaneously determining the 24 elements, has the advantages of simple and rapid operation, greatly saves the detection time, and is efficient and accurate.
Description
Technical Field
The invention relates to the technical field of instrument analysis, in particular to a method for simultaneously measuring the content of 24 element impurities in hydroxyethyl starch sodium chloride injection.
Background
The hydroxyethyl starch is prepared by degrading, hydroxyethylating and further processing high molecular weight amylopectin, is a blood volume expander, can be used for improving hemodynamics, microcirculation and oxygen supply functions, or can be used for treating shock caused by massive hemorrhage, burn or other traumas, and is clinically applied as a basic therapy for resisting the shock. The hydroxyethyl starch sodium chloride injection contains balanced electrolyte components, has the characteristics of not changing acid-base balance, supporting gastric perfusion, maintaining renal function and the like, is particularly suitable for preventing and treating shock, and has wide clinical application prospect.
In the process of synthesizing and preparing the hydroxyethyl starch sodium chloride injection, raw materials, contact production process components, auxiliary materials, contact packages and the like may contain elements harmful to human bodies, so that the elements can be transferred into medicines. In recent years, the pharmacopoeia of various countries and relevant guidelines put higher demands on elemental impurities, ICH Q3D specifies 24 kinds of elemental impurities to be controlled, which are classified into 4 classes (1, 2A, 2B, 3) according to toxicity and origin, and respectively give different limits (allowable daily exposure, PDE) according to different administration routes (oral administration, injection, inhalation). As for the class 1 elements, the element cadmium has the biological accumulation property, can cause environmental pollution and is harmful to human health. Elemental lead accumulates in human and animal and plant tissues and its major toxic effects are anemia, neurological dysfunction and kidney damage. Trace arsenic can cause cell and capillary poisoning, stimulate hematopoietic organs, and even induce malignant tumors. Elemental mercury destroys the central nervous system and prolonged exposure to high mercury environments can lead to brain damage and death (although mercury has a high boiling point, saturated mercury vapor at room temperature has reached several times the toxic dose).
At present, the research on element impurities in the medicine is less according to the ICH guiding principle, and no related research on hydroxyethyl starch sodium chloride injection is available. Therefore, it is necessary to provide a new and effective analysis method for simultaneously determining 24 kinds of element impurities needing to be controlled in ICH Q3D in hydroxyethyl starch sodium chloride injection.
Disclosure of Invention
The invention aims to provide a method for simultaneously determining the content of 24 element impurities in hydroxyethyl starch sodium chloride injection aiming at the defects in the prior art.
In order to achieve the purpose, the invention adopts the technical scheme that:
the method for simultaneously determining the content of 24 element impurities in hydroxyethyl starch sodium chloride injection is provided, wherein the 24 element impurities comprise: lithium element, vanadium element, chromium element, cobalt element, nickel element, copper element, arsenic element, selenium element, molybdenum element, ruthenium element, rhodium element, palladium element, silver element, cadmium element, tin element, antimony element, barium element, osmium element, iridium element, platinum element, gold element, mercury element, thallium element, and lead element, and the steps include:
s1, taking the standard solution containing the 24 element impurities, diluting the standard solution with a first solvent, and uniformly mixing to obtain a control solution;
s2, taking a mixed internal standard solution containing 6 elements, isopropanol and nitric acid, diluting with a second solvent, and shaking up to obtain an internal standard solution;
s3, taking a sample solution, diluting the sample solution with a first solvent, and shaking up to obtain a test sample solution;
s4, injecting the sample into an inductively coupled plasma mass spectrometer, and detecting by adopting a standard curve method of internal standard correction, namely, the content of 24 element impurities in the hydroxyethyl starch sodium chloride injection can be simultaneously measured;
wherein the first solvent is prepared by diluting nitric acid and hydrochloric acid with a second solvent and uniformly mixing;
wherein the 6 elements include: scandium element, germanium element, yttrium element, indium element, terbium element, and bismuth element;
wherein the second solvent is ultrapure water;
wherein the inductively coupled plasma mass spectrometer conditions include:
an Agilent 8900 inductively coupled plasma mass spectrometer is adopted; mass spectrum mode options are peak shape: 3 point; the number of repetitions was 3; the number of scans/repeats was 100; the tuning mode is a No Gas mode or/and a He mode; the plasma mode is HMI; the plasma power is 1600 w; the carrier gas flow is 0.7L/min-0.8L/min; the compensating gas flow is 0.39L/min-0.5L/min; the flow rate of the helium gas is 0-5.5L/min; the sampling depth is 10.0 mm; the peristaltic pump speed was 0.10 rps; and introducing the internal standard element into the plasma on line through a T-shaped three-way pipe.
Preferably, the 24 elemental impurities include:7Li、51V、52Cr、59Co、60Ni、63Cu、75As、78Se、95Mo、101Ru、103Rh、105Pd 、107Ag、111Cd、118Sn、121Sb、138Ba、189Os、193Ir、195Pt、197Au、202Hg、205tl and208Pb。
preferably, the 6 elements include:45Sc、72Ge、89Y、115In、159tb and209Bi。
further, the air conditioner is provided with a fan,7Li、51V、52cr and75internal standard of As45Sc；59Co、60Ni、63Cu and78internal standard of Se72Ge；95Mo、101Ru and103internal standard of Rh89Y；105Pd、118Sn、121Sb and138internal standard of Ba115In；111Internal standard of Cd159Tb；107Ag、189Os、193Ir、195Pt、197Au、202Hg、205Tl and208internal standard of Pb209Bi。
Further, when the hydroxyethyl starch and the sodium chloride are measured in the injection7At Li content, the tuning mode is the No Gas mode.
Further preferably, when the tuning mode is the No Gas mode, the plasma mode is HMI; the plasma power is 1600 w; the carrier gas flow is 0.8L/min; the flow rate of the compensation gas is 0.39L/min.
Further, when the hydroxyethyl starch and the sodium chloride are measured in the injection51V、52Cr、59Co、60Ni、63Cu、75As、78Se、95Mo、101Ru、103Rh、105Pd、107A g、111Cd、118Sn、121Sb、138Ba、189Os、193Ir、195Pt、197Au、202Hg、205Tl or208And when the content of Pb is higher than that of the Pb, the tuning mode is the He mode.
Further preferably, when the tuning mode is the He mode, the plasma mode is HMI; the plasma power is 1600 w; the carrier gas flow is 0.7L/min; the flow rate of the compensating gas is 0.5L/min; the flow rate of the helium gas was 5.5L/min.
Through above-mentioned technical scheme, carrier gas flow is the important parameter that improves the appearance volume of advancing, and the stability of appearance is advanced will further improve to the compensation gas flow, can optimize sensitivity through adjusting carrier gas flow and compensation gas flow.
By adopting the technical scheme, compared with the prior art, the invention has the following technical effects:
the method for simultaneously determining the content of the impurities of the 24 elements in the hydroxyethyl starch sodium chloride injection improves the stability of low-concentration Hg by optimizing a sample processing method and using a first solvent as a diluent and a standard solution to prepare the solvent, reduces the sensitization effect of organic matters by adding a proper amount of isopropanol into an internal standard solution, overcomes the interference of the organic matters, optimizes instrument parameters, formulates the method capable of simultaneously determining the 24 elements, has the advantages of simple and rapid operation, greatly saves the detection time, and is efficient and accurate.
Drawings
FIG. 1 is a mass spectrum of lithium impurity obtained by implementing the method of the present invention;
fig. 2 is a mass spectrum diagram of impurities of vanadium, chromium, cobalt, nickel, copper, arsenic, selenium, molybdenum, ruthenium, rhodium, palladium, silver, cadmium, tin, antimony, barium, osmium, iridium, platinum, gold, mercury, thallium, and lead obtained by implementing the method of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without inventive exercise, are within the scope of the present invention.
It should be noted that, in the case of no conflict, the embodiments and features in the embodiments of the present invention may be combined with each other; the experimental operations in the following examples are all conventional operations unless otherwise specified; materials, reagents and the like used in the following examples are commercially available from public unless otherwise specified.
The invention is further described with reference to the following figures and specific examples, which are not intended to be limiting.
Examples
As shown in fig. 1, this embodiment provides a method for simultaneously determining the content of 24 elemental impurities in hydroxyethyl starch sodium chloride injection, where the 24 elemental impurities include: lithium element (b)7Li), vanadium element (51V), chromium elementSu (b)52Cr), cobalt element (b)59Co), nickel element(s) ((II)60Ni), copper element(s) <63Cu), As element(s) ((ii)75As), selenium element (78Se), molybdenum element(s) (95Mo), ruthenium element(s) (101Ru), rhodium element (II)103Rh), palladium element(s) ((II)105Pd), silver element (C)107Ag and cadmium element (C)111Cd, tin element (b)118Sn), antimony element (b)121Sb) and barium element (138Ba), osmium element (189Os), Iridium element(s)193Ir), platinum element(s) <195Pt), gold element(s) (197Au), mercury element(s) ((ii)202Hg), thallium element (205Tl) and lead element(s) (208Pb), comprising the steps of:
s1-1, respectively measuring 1.0mL of a mixed standard solution (the concentration of each element is 100 mu g/mL) containing lithium, vanadium, chromium, cobalt, nickel, copper, arsenic, selenium, molybdenum, ruthenium, rhodium, palladium, cadmium, tin, antimony, barium, iridium, platinum, gold, mercury, thallium and lead, diluting with a first solvent to a constant volume of 100mL, and mixing uniformly to obtain a control stock solution with the concentration of each element being 1000 ng/mL;
s1-2, respectively measuring appropriate amount of the reference stock solutions, diluting with a first solvent, and uniformly mixing to obtain reference solutions with corresponding use concentrations, wherein the specific standard curve concentrations of each level are shown in Table 1;
TABLE 1
S2, measuring 10mL of scandium-containing elements (45Sc), germanium element(s) ((S)72Ge), yttrium element(89Y), indium element(s) <115In), terbium element(s) (159Tb and bismuth element(s) (II)209Bi), 20mL of isopropanol and 2mL of nitric acid, diluting with a second solvent to a volume of 100mL, and shaking up to obtain an internal standard solution with the concentration of each element of 1000 ng/mL;
s3, taking 10mL of hydroxyethyl starch and sodium chloride injection (500 mL: 30g of hydroxyethyl starch (200/0.5) and 4.5g of sodium chloride), diluting with a first solvent to a constant volume of 25mL, and shaking up to obtain a test sample solution;
s4, injecting the sample into an inductively coupled plasma mass spectrometer, and detecting by adopting a standard curve method of internal standard correction, namely, the content of 24 element impurities in the hydroxyethyl starch sodium chloride injection can be simultaneously measured;
wherein the first solvent is prepared by diluting 10mL of nitric acid and 10mL of hydrochloric acid to 1L by using a second solvent and uniformly mixing;
wherein the second solvent is ultrapure water;
wherein the inductively coupled plasma mass spectrometer conditions include:
an Agilent 8900 inductively coupled plasma mass spectrometer (the inductively coupled plasma mass spectrometer can be set to select different tuning modes for simultaneous measurement); mass spectrum mode options are peak shape: 3 point; the number of repetitions was 3; the number of scans/repeats was 100; selecting two tuning modes of a No Gas mode and a He mode simultaneously;
when the hydroxyethyl starch and the sodium chloride are measured in the injection7When the content of Li is high, the tuning mode is a No Gas mode; the plasma mode is HMI; the plasma power is 1600 w; the carrier gas flow is 0.8L/min; the compensating air flow is 0.39L/min;
when the hydroxyethyl starch and the sodium chloride are measured in the injection51V、52Cr、59Co、60Ni、63Cu、75As、78Se、95Mo、101Ru、103Rh、105Pd、107A g、111Cd、118Sn、121Sb、138Ba、189Os、193Ir、195Pt、197Au、202Hg、205Tl or208When the content of Pb is high, the tuning mode is He mode; the plasma mode is HMI; the plasma power is 1600 w; the carrier gas flow rate is 0.7L/min; the compensating air flow is 0.5L/min; the flow rate of the helium gas is 5.5L/min;
the sampling depth is 10.0 mm; the peristaltic pump speed was 0.10 rps; the internal standard element is introduced into the plasma on line through a T-shaped three-way pipe.
In a preferred embodiment of the present invention,7Li、51V、52cr and75internal standard of As45Sc；59Co、60Ni、63Cu and78internal standard of Se72Ge；95Mo、101Ru and103internal standard of Rh89Y；105Pd、118Sn、121Sb and138internal standard of Ba115In；111Internal standard of Cd159Tb；107Ag、189Os、193Ir、195Pt、197Au、202Hg、205Tl and208internal standard of Pb209Bi。
Detection examples
The detection embodiment considers the linearity, detection limit, quantitative limit, recovery rate and repeatability of the method for simultaneously determining the content of the 24 element impurities in the hydroxyethyl starch sodium chloride injection as shown in the embodiment; the results of linearity, detection limit and quantitation limit are shown in Table 2, and the results of recovery and reproducibility are shown in Table 3. Therefore, the method provided by the invention is simple and convenient to operate, good in sensitivity and high in accuracy.
TABLE 2
TABLE 3
In conclusion, the method for simultaneously determining the content of the impurities of the 24 elements in the hydroxyethyl starch sodium chloride injection provided by the invention optimizes the sample processing method, uses the first solvent as the diluent and the standard solution to prepare the solvent, improves the stability of low-concentration Hg, adds a proper amount of isopropanol into the internal standard solution, reduces the sensitization effect of organic matters, overcomes the interference of the organic matters, optimizes instrument parameters, formulates the method capable of simultaneously determining the 24 elements, has the advantages of simple and rapid operation, greatly saves the detection time, and has high efficiency and accuracy.
While the invention has been described with reference to a preferred embodiment, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention.
Claims (8)
1. A method for simultaneously determining the content of 24 element impurities in hydroxyethyl starch sodium chloride injection, wherein the 24 element impurities comprise: the lead-free copper-based alloy material is characterized by comprising lithium, vanadium, chromium, cobalt, nickel, copper, arsenic, selenium, molybdenum, ruthenium, rhodium, palladium, silver, cadmium, tin, antimony, barium, osmium, iridium, platinum, gold, mercury, thallium and lead, and being characterized by comprising the following steps of:
s1, taking the standard solution containing the 24 element impurities, diluting the standard solution with a first solvent, and uniformly mixing to obtain a control solution;
s2, taking a mixed internal standard solution containing 6 elements, isopropanol and nitric acid, diluting with a second solvent, and shaking up to obtain an internal standard solution;
s3, taking a sample solution, diluting the sample solution with a first solvent, and shaking up to obtain a test sample solution;
s4, injecting the sample into an inductively coupled plasma mass spectrometer, and detecting by adopting a standard curve method of internal standard correction, namely, the content of 24 element impurities in the hydroxyethyl starch sodium chloride injection can be simultaneously measured;
wherein the first solvent is prepared by diluting nitric acid and hydrochloric acid with a second solvent and uniformly mixing;
wherein the 6 elements include: scandium element, germanium element, yttrium element, indium element, terbium element, and bismuth element;
wherein the second solvent is ultrapure water;
wherein the inductively coupled plasma mass spectrometer conditions include:
an Agilent 8900 inductively coupled plasma mass spectrometer is adopted; mass spectrum mode options are peak shape: 3 point; the number of repetitions was 3; the number of scans/repeats was 100; the tuning mode is a No Gas mode or/and a He mode;
the plasma mode is HMI; the plasma power is 1600 w; the carrier gas flow is 0.7L/min-0.8L/min; the compensating gas flow is 0.39L/min-0.5L/min; the flow rate of the helium gas is 0-5.5L/min; the sampling depth is 10.0 mm; the peristaltic pump speed was 0.10 rps; and introducing the internal standard element into the plasma on line through a T-shaped three-way pipe.
2. The method of claim 1, wherein the 24 elemental impurities comprise:7Li、51V、52Cr、59Co、60Ni、63Cu、75As、78Se、95Mo、101Ru、103Rh、105Pd、107Ag、111Cd、118Sn、121Sb、138Ba、189Os、193Ir、195Pt、197Au、202Hg、205tl is represented byAnd208Pb。
3. the method of claim 1, wherein the 6 elements comprise:45Sc、72Ge、89Y、115In、159tb and209Bi。
4. the method according to claim 2 or 3,7Li、51V、52cr and75internal standard of As45Sc；59Co、60Ni、63Cu and78internal standard of Se72Ge；95Mo、101Ru and103internal standard of Rh89Y；105Pd、118Sn、121Sb and138internal standard of Ba115In；111Internal standard of Cd159Tb；107Ag、189Os、193Ir、195Pt、197Au、202Hg、205Tl and208internal standard of Pb209Bi。
5. The method of claim 2, wherein the hydroxyethyl starch sodium chloride injection is measured7At Li content, the tuning mode is the No Gas mode.
6. The method of claim 5, wherein when the tuning mode is the No Gas mode, the plasma mode is HMI; the plasma power is 1600 w; the carrier gas flow is 0.8L/min; the flow rate of the compensation gas is 0.39L/min.
7. The method of claim 2, wherein the hydroxyethyl starch sodium chloride injection is measured51V、52Cr、59Co、60Ni、63Cu、75As、78Se、95Mo、101Ru、103Rh、105Pd、107Ag、111Cd、118Sn、121Sb、138Ba、189Os、193Ir、195Pt、197Au、202Hg、205Tl or208And when the content of Pb is higher than that of the Pb, the tuning mode is the He mode.
8. The method of claim 5, wherein when the tuning mode is the He mode, the plasma mode is HMI; the plasma power is 1600 w; the carrier gas flow is 0.7L/min; the flow rate of the compensating gas is 0.5L/min; the flow rate of the helium gas was 5.5L/min.
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