DE2156604A1 - Control standard for liquid blood serum - Google Patents
Control standard for liquid blood serumInfo
- Publication number
- DE2156604A1 DE2156604A1 DE19712156604 DE2156604A DE2156604A1 DE 2156604 A1 DE2156604 A1 DE 2156604A1 DE 19712156604 DE19712156604 DE 19712156604 DE 2156604 A DE2156604 A DE 2156604A DE 2156604 A1 DE2156604 A1 DE 2156604A1
- Authority
- DE
- Germany
- Prior art keywords
- serum
- resin
- per
- sodium
- solvent
- 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
- 210000002966 serum Anatomy 0.000 title claims description 67
- 239000007788 liquid Substances 0.000 title claims description 14
- 239000002904 solvent Substances 0.000 claims description 19
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 18
- 239000011347 resin Substances 0.000 claims description 16
- 229920005989 resin Polymers 0.000 claims description 16
- 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 claims description 13
- 238000000034 method Methods 0.000 claims description 13
- 239000011734 sodium Substances 0.000 claims description 13
- 210000002381 plasma Anatomy 0.000 claims description 11
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 10
- 239000011591 potassium Substances 0.000 claims description 10
- 229910052708 sodium Inorganic materials 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 8
- 102000004895 Lipoproteins Human genes 0.000 claims description 6
- 108090001030 Lipoproteins Proteins 0.000 claims description 6
- 239000003729 cation exchange resin Substances 0.000 claims description 6
- 239000003456 ion exchange resin Substances 0.000 claims description 6
- 229920003303 ion-exchange polymer Polymers 0.000 claims description 6
- 229910001415 sodium ion Inorganic materials 0.000 claims description 6
- 239000004793 Polystyrene Substances 0.000 claims description 5
- 230000002378 acidificating effect Effects 0.000 claims description 5
- 229920002223 polystyrene Polymers 0.000 claims description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 5
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 4
- 229910001424 calcium ion Inorganic materials 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 229910001414 potassium ion Inorganic materials 0.000 claims description 4
- 239000003146 anticoagulant agent Substances 0.000 claims description 3
- 229940127219 anticoagulant drug Drugs 0.000 claims description 3
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims description 3
- 238000000605 extraction Methods 0.000 claims description 3
- 125000000542 sulfonic acid group Chemical group 0.000 claims description 3
- BOSAWIQFTJIYIS-UHFFFAOYSA-N 1,1,1-trichloro-2,2,2-trifluoroethane Chemical compound FC(F)(F)C(Cl)(Cl)Cl BOSAWIQFTJIYIS-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- UUCCCPNEFXQJEL-UHFFFAOYSA-L strontium dihydroxide Chemical compound [OH-].[OH-].[Sr+2] UUCCCPNEFXQJEL-UHFFFAOYSA-L 0.000 claims description 2
- 229910001866 strontium hydroxide Inorganic materials 0.000 claims description 2
- PFRGGOIBYLYVKM-UHFFFAOYSA-N 15alpha-hydroxylup-20(29)-en-3-one Natural products CC(=C)C1CCC2(C)CC(O)C3(C)C(CCC4C5(C)CCC(=O)C(C)(C)C5CCC34C)C12 PFRGGOIBYLYVKM-UHFFFAOYSA-N 0.000 claims 1
- SOKRNBGSNZXYIO-UHFFFAOYSA-N Resinone Natural products CC(=C)C1CCC2(C)C(O)CC3(C)C(CCC4C5(C)CCC(=O)C(C)(C)C5CCC34C)C12 SOKRNBGSNZXYIO-UHFFFAOYSA-N 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 12
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 9
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 9
- 229960001031 glucose Drugs 0.000 description 9
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 8
- 229960005069 calcium Drugs 0.000 description 8
- 239000011575 calcium Substances 0.000 description 8
- 229910052791 calcium Inorganic materials 0.000 description 8
- 239000000463 material Substances 0.000 description 8
- 229910052700 potassium Inorganic materials 0.000 description 8
- -1 ammonium ions Chemical class 0.000 description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 6
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 229940109239 creatinine Drugs 0.000 description 6
- 239000008103 glucose Substances 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 239000000523 sample Substances 0.000 description 6
- 229940116269 uric acid Drugs 0.000 description 6
- PNNCWTXUWKENPE-UHFFFAOYSA-N [N].NC(N)=O Chemical compound [N].NC(N)=O PNNCWTXUWKENPE-UHFFFAOYSA-N 0.000 description 5
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 239000001509 sodium citrate Substances 0.000 description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 102000009027 Albumins Human genes 0.000 description 3
- 108010088751 Albumins Proteins 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- 102000003929 Transaminases Human genes 0.000 description 3
- 108090000340 Transaminases Proteins 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 229940023913 cation exchange resins Drugs 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 2
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229960002713 calcium chloride Drugs 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 239000001569 carbon dioxide Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 150000002576 ketones Chemical class 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000010421 standard material Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 229940034208 thyroxine Drugs 0.000 description 2
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 description 2
- 229940045136 urea Drugs 0.000 description 2
- AJDIZQLSFPQPEY-UHFFFAOYSA-N 1,1,2-Trichlorotrifluoroethane Chemical compound FC(F)(Cl)C(F)(Cl)Cl AJDIZQLSFPQPEY-UHFFFAOYSA-N 0.000 description 1
- ZJQIXGGEADDPQB-UHFFFAOYSA-N 1,2-bis(ethenyl)-3,4-dimethylbenzene Chemical group CC1=CC=C(C=C)C(C=C)=C1C ZJQIXGGEADDPQB-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000002260 Alkaline Phosphatase Human genes 0.000 description 1
- 108020004774 Alkaline Phosphatase Proteins 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- 239000004382 Amylase Substances 0.000 description 1
- 102000013142 Amylases Human genes 0.000 description 1
- 108010065511 Amylases Proteins 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 229920000209 Hexadimethrine bromide Polymers 0.000 description 1
- HBBGRARXTFLTSG-UHFFFAOYSA-N Lithium ion Chemical compound [Li+] HBBGRARXTFLTSG-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 description 1
- QILXPCHTWXAUHE-UHFFFAOYSA-N [Na].NCCN Chemical compound [Na].NCCN QILXPCHTWXAUHE-UHFFFAOYSA-N 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 235000019418 amylase Nutrition 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000013060 biological fluid Substances 0.000 description 1
- 239000012472 biological sample Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 229940107161 cholesterol Drugs 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- UMNKXPULIDJLSU-UHFFFAOYSA-N dichlorofluoromethane Chemical compound FC(Cl)Cl UMNKXPULIDJLSU-UHFFFAOYSA-N 0.000 description 1
- IRXRGVFLQOSHOH-UHFFFAOYSA-L dipotassium;oxalate Chemical compound [K+].[K+].[O-]C(=O)C([O-])=O IRXRGVFLQOSHOH-UHFFFAOYSA-L 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical group FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- SLGWESQGEUXWJQ-UHFFFAOYSA-N formaldehyde;phenol Chemical class O=C.OC1=CC=CC=C1 SLGWESQGEUXWJQ-UHFFFAOYSA-N 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical compound CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 229960001008 heparin sodium Drugs 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 229910001410 inorganic ion Inorganic materials 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229910001416 lithium ion Inorganic materials 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- KHPXUQMNIQBQEV-UHFFFAOYSA-N oxaloacetic acid Chemical compound OC(=O)CC(=O)C(O)=O KHPXUQMNIQBQEV-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- DBSDMAPJGHBWAL-UHFFFAOYSA-N penta-1,4-dien-3-ylbenzene Chemical compound C=CC(C=C)C1=CC=CC=C1 DBSDMAPJGHBWAL-UHFFFAOYSA-N 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 229940061610 sulfonated phenol Drugs 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/96—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood or serum control standard
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J39/00—Cation exchange; Use of material as cation exchangers; Treatment of material for improving the cation exchange properties
- B01J39/04—Processes using organic exchangers
- B01J39/05—Processes using organic exchangers in the strongly acidic form
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2496/00—Reference solutions for assays of biological material
- G01N2496/05—Reference solutions for assays of biological material containing blood cells or plasma
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2496/00—Reference solutions for assays of biological material
- G01N2496/80—Multi-analyte reference solutions containing cholesterol, glucose and the like
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
- Y10T436/102499—Blood gas standard or control
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Description
PATENTANWÄLTEPATENT LAWYERS
dr. W. Schalk · dipl.-ing. P. Wirth · dipl.-ing. G. Dannenberg DR. V. SCHMIED-KOWARZIK · DR. P. WE I N HOLD · DR. D. G U DELdr. W. Schalk dipl.-ing. P. Wirth dipl.-ing. G. Dannenberg DR. V. SCHMIED-KOWARZIK · DR. P. WE I N HOLD · DR. D. G U DEL
6 FRANKFURT AM MAIN GR. ESCHENHEIMER STRASSE 396 FRANKFURT AM MAIN GR. ESCHENHEIMER STRASSE 39
Baxter Laboratories, Inc. Morton Grave, 111. 60053 USABaxter Laboratories, Inc. Morton Grave, 111.60053 United States
SK/SK H-233SK / SK H-233
Kontrallstandard für flüssiges BlutserumControl standard for liquid blood serum
' ■ · i '■ · i
Die vorliegende Erfindung bezieht sich auf eine Kontroll-Standardprobe für flüssiges Blutserum und auf ein Verfahren zur Herstellung derselben.The present invention relates to a control standard sample for liquid blood serum and a method for producing the same.
Blutserum ist eine komplexe biologische Flüssigkeit mit zahlreichen Komponenten von wesentlicher physiologischer Bedeutung. Beim normalen oder durchschnitt-·' liehe gesunden Menschen fallen die Konzentrationen dieser Komponenten innerhalb bestimmte, einigermaßen gut definierte Grenzen. Wenn festgestellt wird, daß eine oder mehrere dieser Komponenten laut Analyse außerhalb dieser annehmbaren Grenzen liegen, sind verschiedene Krankheiten oder pathologische Zustände des Körpersystems angezeigt.Blood serum is a complex biological fluid with numerous components of essential physiological importance. With normal or average- ' For healthy people, the concentrations of these components fall within certain, reasonably well-defined limits. If it is determined that one or more of these components are analyzed outside of these acceptable limits are various diseases or pathological conditions of the body system displayed.
In den letzten Jahren sind verschiedene automatisierta Verfahren zur zweckmäßigen Analyse von Blutserum mit seinen vielen Komponenten entwickelt worden. Einige Analysevorrichtungen für diese Zwecke sind dar "AutoAnalyzer" der Firma Technician, der "Robot Chemist" der Firma Warner Chillcott und der "Discrete Analyzer" der Firma Beckman. Diese Instrumente können schnell und nacheina**. der die Konzentration einer Vidzahl von Blutserunkomponenten in einer einzi« In recent years, various automated methods have been developed for convenient analysis of blood serum and its many components. Some analysis devices for these purposes is "Auto Analyzer" Technician of the company, the "Robot Chemist" of the company Warner Chillcott and the "Discrete Analyzer" Beckman. These instruments can be used quickly and sequentially. the concentration of a number of blood serum components in a single
209823/ 1 091209823/1 091
gen Probe, d.h. z.B. bis zu ein Dutzend oder mehr Werte, bestimmen.Determine the sample, i.e. e.g. up to a dozen or more values.
Bei der Durchführung der analytischen Tests von Blutserum und anderen biologischen Proben mit den obigen und ähnlichen Vorrichtungen müssen Laboratoriuras-Standardmaterialien oder sog. "Bezugs- oder Kontrollstandards" verwendet werden, um das Instrument zu kalibrieren und zu kontrollieren. Genaue Ergebnisse bei der Verwendung dieser Lnstrumente, insbesondere im Fall einea vielfach automatisierten Verfahrens, hängen von der scharfen und ständigen Standardisierung der biochemischen Bestimmungen ab.In performing the analytical tests on blood serum and other biological samples with the above and similar devices, Laboratoriuras standard materials or so-called "reference or control standards" must be used to calibrate and control the instrument. Accurate results in the use of these instruments, especially in the case of a multiple automated procedures, depend on strict and constant standardization of biochemical determinations.
Ein Beispiel der in der Praxis verwendeten Kontrollstandards ist das gefriergetrocknete Serum, das vor der Verwendung mit wässrigem Ammoniumbicarbonat rekonstituiert wird (vgl. die US-Patentschrift 3 466 249). Für bestimmte Zwecke wäre jedoch eine vollständige flüssige Kontrollstandardprobe, die keine derartige Rekonstituierung erforderte, zweckmäßig; sie könnte in der Praxis eine weitgehende Verwendung finden.An example of the control standards used in practice is the freeze-dried serum, which is mixed with aqueous ammonium bicarbonate before use is reconstituted (see U.S. Patent 3,466,249). For specific purposes however, a complete liquid control standard sample that did not require such reconstitution would be useful; in practice it could be one find widespread use.
Ziel der vorliegenden Erfindung ist daher die Schaffung einer flüssigen Blutserum-Kontrollstandardprobe.It is therefore an object of the present invention to provide a liquid blood serum control standard sample.
Ein weiteres Ziel ist die Schaffung eines stabilen Blutserumbezugsstandards, Bk- der zur direkten Kalibierung und Kontrolle von mehrfach automatisierten Analyseverfahren verwendet werden kann.Another goal is to create a stable blood serum reference standard, Bk- which can be used for direct calibration and control of multiple automated analysis processes.
Erfindungsgemäß wird nun flüssiges Blutserum mit einem stark sauren Kationenaustauscherharz zur Verringerung des Natrium», Kalium- und Calciurespiegels im Serum behandelt, und der pH-Wert des Serums »irri durch ausreichend alkalisches Reagenz, das keinerlei Natrium-, Kalium-, Calcium- oder Ammoniumionen enthält, auf etwa seinem ursprünglichen Wert Behalten oder wieder eingestellt. Dann wird das mit Harz behandelte und in seinem pH-Wert eingestellte Serum getrocknet:,According to the invention, liquid blood serum is now mixed with a strongly acidic cation exchange resin to reduce the sodium, potassium and calcium levels in the Serum treated, and the pH of the serum »irri by sufficiently alkaline Reagent that does not contain any sodium, potassium, calcium or ammonium ions, Retained or reinstated at approximately its original value. Then it will be the serum treated with resin and adjusted in its pH value dried :,
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und die LipoprotBlnkomponente wird mit einem Fettlösungsmittel extrahiert. Das Serum, das dadurch praktisch frei von Lipoprotein ist, wird mit Wasser rekonstituiert, um ein flüssiges Grund-Blutserum zu ergeben. In Abhängigkeit Von der Analyse der Ausgangsmaterials und der gewünschten Konzentration der verschiedenen Komponenten im Endprodukt können diesem flüssigen Grund-Blutssruni Materialien zur Schaffung des endgültigen Kontröllstandards zugegeben werden.and the lipoprotein component is extracted with a fat solvent. The serum, which is practically free of lipoprotein, is mixed with water reconstituted to give a liquid basic blood serum. Dependent on From the analysis of the starting material and the desired concentration of the Various components in the final product can cause this basic liquid blood flow Materials may be added to create the final control standard.
Das Verfahren zur Herstellung des erfindungsgemäßen flüssigen Blutserumkontrollstandards eignet sich besonders zur Verwendung mit defibriniertem Blutplasma mit hohen Konzentrationen der anorganischen Ionen:Natrium, Kalium und Calcium, wie z.B. gelagertes Blutplasma mit den Antikoagulationsmitteln Natriumeitrat, Kaliumoxalat, Heparinnatrium oder Natriumäthylendiamintetra- " acetat, citriertes Blutplasma (das Natriumeitrat oder Natriumeitrat und Dextrose enthält) ACD Blutplasma (mit Zitronensäure, Natriumeitrat und Dextrose) und CPD Blutplasma (mit Citrat, Phosphat und Dextrose).The method for the preparation of the liquid blood serum control standard according to the invention is particularly suitable for use with defibrinated blood plasma with high concentrations of inorganic ions: sodium, potassium and calcium such as stored blood plasma with the anticoagulants Sodium citrate, potassium oxalate, heparin sodium or sodium ethylenediamine tetra- " acetate, citrated blood plasma (the sodium citrate or sodium citrate and dextrose contains) ACD blood plasma (with citric acid, sodium citrate and dextrose) and CPD blood plasma (with citrate, phosphate and dextrose).
Die Defibrination erfolgt, indem man z.B. Calciumionen zum citrierten Blut oder "Polybrene" (Warenzeigen für Hexadimethrenbromid) zu heparinisiertem Blut zufügt.Defibrination is carried out by adding calcium ions, for example, to the citrated blood or "Polybrene" (trademark for hexadimethrene bromide) to heparinized Inflicts blood.
Beispiele der erfindungsgemäß verwendbaren stark sauren Kationenaustauscher— harze sind die Sulfonsäurekationenaustauscherharze. Diese Harze können z.B. ä sulfoniertes Phenol, sulfoniertes Polystyrol, sulfoniertes Phenolformaldehyd, sulfonierte Mischpolymerisate aus aromatischen Monoalkenylkohlenwasserstoffen mit etwa 0,5-25 Gew.-% einer vernetzenden Dialkenylkomponente, z.B. Divinylbsnzöl, Divinyltoluol, Divinylxylol und ähnliche Harze, sein. Derartige Harze sind unter den Warenzeichen "Dowex SO (Dow Chemical Co.), "Amberlite IR-120" (Rohm & Haas Co., Inc.), "Driolite C-3" (Chemical Process Co., Inc.) undExamples of the strongly acidic cation exchange resins which can be used according to the invention are the sulfonic acid cation exchange resins. These resins may for example, like sulfonated phenol, sulfonated polystyrene, sulfonated phenol-formaldehyde, sulfonated copolymers of monoalkenyl aromatic hydrocarbons having from about 0.5-25 wt .-% of a crosslinking Dialkenylkomponente such Divinylbsnzöl, divinyltoluene, divinylxylene and similar resins to be. Such resins are under the trademarks "Dowex SO (Dow Chemical Co.)," Amberlite IR-120 "(Rohm & Haas Co., Inc.)," Driolite C-3 "(Chemical Process Co., Inc.) and
2 09823/109 52 09823/109 5
"Diaion SK Nr. 1" (Mitsubishi Chemical Industries Ltd.) im Hendel erhältlich. Ein bevorzugtes Harz ist "Dowex 50"; diesBS ist ein sulfoniertes, mit Divinylbenzol vernetztes Polystyrol gemäß der US-Patentschrift 2 366 007."Diaion SK No. 1" (Mitsubishi Chemical Industries Ltd.) available from Hendel. A preferred resin is "Dowex 50"; This BS is a sulfonated one with divinylbenzene crosslinked polystyrene according to U.S. Patent 2,366,007.
Andere, erfindungsgemäß verwendbare stark saure Kationenaustauscherharze sind dem Fachmann geläufig und können gemäß Kunin "Ion Exchange Resins", John Wiley & Sons, Inc., New York, 1950, hergestellt werden.Other strongly acidic cation exchange resins which can be used according to the invention are familiar to the person skilled in the art and can according to Kunin "Ion Exchange Resins", John Wiley & Sons, Inc., New York, 1950.
Ein bevorzugtes Harz ist ein Ionenaustauscherharz auf der Basis von Polystyrol mit-kerngebundenen Sulfonsäuregruppen im H'-Zustand, wie z.B. "Dowex-50" mit 50-100 mesh.A preferred resin is an ion exchange resin based on polystyrene with nucleated sulfonic acid groups in the H 'state, such as "Dowex-50" with 50-100 mesh.
Das Blutserum wird mit dem Ionenaustauscherharz vorzugsweise in Anteilen von etwa 25-100 g Harz p. .5 1 Serum gemischt. So können z.B. etwa 40 g "Dowex 50" mit 1 1 Serum gemischt werden; so werden ausgezeichnete Ergebnisse erzielt, wodurch des Natriumionenspiegel von einem Bereich von etwa 165-205 Mill!äquivalenten pro 1 Serum auf etwa 90-95 Milliäquivalente pro 1 Serum verringert wird.The blood serum is preferably in proportions of the ion exchange resin about 25-100 g resin p. .5 1 serum mixed. For example, about 40 g of "Dowex 50" to be mixed with 1 l of serum; thus excellent results are obtained, reducing the sodium ion level from a range of about 165-205 million equivalents per 1 serum reduced to about 90-95 milliequivalents per 1 serum will.
Ein bevorzugtes alkalisches Reagenz, um den pH-Wert des Serums etwa auf seinem ursprünglichen Wert zu halten oder auf diesen einzustellen, ist ein Tris— Puffer /Jri—(hydroxymethyl)—aminomethany . Der Tris-Puffer ist vorzugsweise eine wässrige Lösung aus etwa 30-50 g Tris-verbindung pro 1 dest. Wasser und hat einen pH-Wert von etwa 5,8-6,8 vor dem Trocknen.A preferred alkaline reagent to keep the serum pH around its To keep the original value or to adjust it to this is a tris- Buffer / jri- (hydroxymethyl) -aminomethany. The Tris buffer is preferably one aqueous solution of about 30-50 g Tris compound per 1 dist. Water and has a pH of about 5.8-6.8 before drying.
Gemäß einer Ausführungsform der vorliegenden Erfindung ist eine wichtige, im Kontrollstandard zu enthaltende Blutkoraponente der Harnstoffstickstoff oder Blutharnstoffstickstoff (BUN). Der Blutharnstoffstickstoff kann vorzugsweise nach dem Bertholet-Test oder einen modifizierten Bertholet-Test gemäß den US-Patentschriften 3 119 751, 3 467 499 und Re-issue 26 125According to one embodiment of the present invention, an important im Control standard to contain blood coraponents of urea nitrogen or Blood urea nitrogen (BUN). The blood urea nitrogen can preferably according to the Bertholet test or a modified Bertholet test according to the US patents 3 119 751, 3 467 499 and Re-issue 26 125
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bestimmt werden. Es wurde jedoch gefunden, daß die Verwendung von Trips-Puffer die Bestimmung des Blutharnstoffstickstoffes nach dem Bertholet— oder modifizierten Bertholet-Test stört. Überraschenderweise stört die Verwendung von. Lithiumhydroxyd oder Strontiumhydraxyd diese BUN-Tests nicht, wobei gleichzeitig der Vorteil erzielt wird, daß der Tris-Puffer frei von Kalium-, Natrium-·, to be determined. However, it has been found that the use of Trips Buffer interferes with the determination of blood urea nitrogen according to the Bertholet or modified Bertholet test. Surprisingly, the use of. Lithium hydroxide or strontium hydroxide do not pass these BUN tests, whereby at the same time the advantage is achieved that the Tris buffer is free of potassium, sodium,
ist. .
Calcium- und Ammoniumionen/ Das erfindungsgemäß bevorzugt verwendete Lithium-is. .
Calcium and ammonium ions / The lithium ion preferably used according to the invention
hydroxyd ist eine wässrige Lösung aus etwa 5Q-7Q gj Lithiumhydroxyd pro 1 dest.hydroxyd is an aqueous solution of about 5Q-7Q gj lithium hydroxide per 1 dist.
Wasser.Water.
Das Trocknen des mit Harz behandelten und in seinem pH-Wert eingestellten Serums erfolgt vorzugsweise durch übliche Gefriertrocknungs- oder Lyophilisie- g rungsverfahren, in welchen das Serum aus dem gefrorenen Zustand unter Hochvakuum getrocknet wird und Eis oder ein anderes gefrorenes Lösungsmittel schnell sublimiert, wodurch ein poröser Feststoff erhalten wird.The drying of the serum treated with resin and adjusted in its pH value is preferably carried out by conventional freeze-drying or Lyophilisie- g approximation methods in which the serum from the frozen state under high vacuum dried and rapidly sublimated ice or other frozen solvent to give a porous solid is obtained.
Dann wurd der Lipoproteingehalt des getrockneten Serums durch Extraktion mit einem Fettlösungsmittel entfernt. Erfindungsgemäß verwendbare Fettlösungsmittel sind organische Lösungsmittel,, wie Ester, Äther, Ketone, Kohlenwasserstoffe und chlorierte Kohlenwasserstoffe. Die organischen Lösungsmittel sind z.B. Kohlenwasserstoffe, wie leichte paraffinische Erdölfraktionen oder Naphthas, insbesondere vom Hexan- oder Heptan-Typ, cyclische Kohlenwasserstoffe, wie ä\ Cyclohexan, chlorierte Lösungsmittel, wie Chloroform und Tetrachlorkohlenstoff, Äther, wie Diäthyläther, und Ketone, wie Aceton und Butanon. Ein bevorzugtes Fettlösungsmittel ist ein Fluorkohlenstoff oder "Freon", wie Monofluortrichlormethan, Dichlordifluormethan, Monochlordifluorraethan, Monofluordichlormethan und die verschiedenen Mischungen derselben.Then the lipoprotein content of the dried serum was removed by extraction with a fat solvent. Fat solvents which can be used according to the invention are organic solvents such as esters, ethers, ketones, hydrocarbons and chlorinated hydrocarbons. The organic solvents are, for example hydrocarbons such as light paraffinic petroleum fractions or naphthas, particularly from hexane or heptane type, cyclic hydrocarbons such as ä \ cyclohexane, chlorinated solvents such as chloroform and carbon tetrachloride, ethers such as diethyl ether, and ketones such as acetone and Butanone. A preferred fat solvent is a fluorocarbon or "freon" such as monofluorotrichloromethane, dichlorodifluoromethane, monochlorodifluorraethane, monofluorodichloromethane, and the various mixtures thereof.
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Die Lösungsmittelextraktion erfolgt durch gründliches Mischen des getrocknacsn Serums mit dem Fettlösungsmittel und anschließendes Abtrennung des ungelösten Materials vom Fettlösungsmittel. Das getrocknete Serum wird mit dem Lösungsmittel vorzugsweise'in Verhältnissen von etwa 30-90 g Serum pro 1 Lösungsmittel für etwa 10-60 Minuten unter Rühren gemischt. Das Fettlösungsmittel kann abfiltriert oder durch ähnliche Verfahren entfernt werden, wobei irgendwelches verbleibendes Lösungsmittel von den erhaltenen trockenen Serumteilchen abdampfen gelassen wird.Solvent extraction is done by thoroughly mixing the getrocknacsn Serum with the fat solvent and subsequent separation of the undissolved Materials from the fat solvent. The dried serum is mixed with the solvent mixed preferably in proportions of about 30-90 g serum per liter of solvent for about 10-60 minutes with stirring. The fat solvent can be filtered off or removed by similar procedures, with any remaining solvent from the resulting dry serum particles is allowed to evaporate.
Das Serum, das denn praktisch frei von Lipoprotein ist, wird dann mit Wasser, vorzugsweise dest. Wasser, auf etwa sein ursprüngliches Volumen odBr in anderen geeigneten Verhältnissen rekonstituiert, wodurch man den Konstrollstandard aus flüssigem Grund-Blutserum erhält.The serum, which is practically free of lipoprotein, is then mixed with water, preferably least. Water, to about its original volume odBr in reconstituted in other appropriate proportions, thereby setting the standard of control obtained from liquid basic blood serum.
Blutserumkomponenten, die in den erfindungsgeraäßen Kantrollstandard einverleibt werden können, sind Substanzen aus der Gruppe von Albumin, Säurephospha— tase, alkalische Phosphatase, Amylase, .Bilirubin, Calcium, Kohlendioxyd, · Chlorid, Cholesterin, Creatinin, Glucose, Hämoglobin, Milchsäuredehydrogenass, Phosphor, Kalium, Natrium, Gesamtprotein, Transaminasen, wie Seruraglutaminoxalessigsäuretransaminase und Serumglutaminbrenztraubensäuretransaminase, Triglyceride, Harnstoffstickstoff, Harnsäure und andere derartige Substanzen des Blutserums.Blood serum components that are incorporated into the Kantroll standard according to the invention are substances from the group of albumin, acid phosphate- tase, alkaline phosphatase, amylase, bilirubin, calcium, carbon dioxide, Chloride, cholesterol, creatinine, glucose, hemoglobin, lactic acid dehydrogenase, Phosphorus, potassium, sodium, total protein, transaminases such as seruraglutamine oxaloacetic acid transaminase and serum glutamine pyruvic transaminase, triglycerides, urea nitrogen, uric acid and other such substances of the blood serum.
Ein erfindungsgemäß bevorzugter Kantrollstandard enthält vorherbestimmte Konzentrationen der folgenden Blutserumkomponenten in einer Mischung: Natrium, Kalium, Chlorid, Phosphor, Calcium, BUN, Glucose, Harnsäure, Creatinin, Gesaatprotein, proteingebundenes Jod (PBlJ und Kohlendioxyd (HCO3"). Des flüssig» Grundserum kann auf die gewünschten, vorherbestimmten Werte dieser Komponenten gebracht werden, indem man geeignete Mengen der entsprechenden, die Korapo—A Kantroll standard preferred according to the invention contains predetermined concentrations of the following blood serum components in a mixture: sodium, potassium, chloride, phosphorus, calcium, BUN, glucose, uric acid, creatinine, seed protein, protein-bound iodine (PBlJ and carbon dioxide (HCO 3 "). The liquid" basic serum can be brought to the desired, predetermined values of these components by adding suitable amounts of the corresponding, the Korapo—
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nenten enthaltenden Materialien zufügt. Für die 12 obigen Blutserumkomponenten können jeweils die folgenden Materialien zugegeben werden: Natriumacetat, Kaliumhydroxyd, Natriumchlorid, Kaliumdihydrogenphosphat, Calciumchlorid, Hernstoff, Glucose, Harnsäure, Creatinin, getrocknetes Blutserum, Thyroxin und Natriumbicarbonat. Dieser Kontrollstandard ist unter üblichen Kühltemperaturen (4 C.) für 3 Monate lagerungsbeständigkeit und liefert geeignete Bestimmungs— werte für die genannten Komponenten.nenten-containing materials adds. For the 12 above blood serum components the following materials can be added: sodium acetate, potassium hydroxide, sodium chloride, potassium dihydrogen phosphate, calcium chloride, Urea, glucose, uric acid, creatinine, dried blood serum, thyroxine and Sodium bicarbonate. This control standard is below normal refrigeration temperatures (4 C.) Storage stability for 3 months and provides suitable determination values for the components mentioned.
Die folgenden Beispiele veranschaulichen die vorliegende Erfindung, ohne sie zu beschränken.The following examples illustrate the present invention without it to restrict.
Citriertes menschliches Blutserum wurde durch Zugabe von Calciumionen und an- " schließendes Filtrieren defibriniert. Dann wurde das erhaltene Serum mit einem Polystyrolionenaustauscherharz mit kerrigebundsnen Sulfonsäuregruppen ("Dowex 50"j 50—100 mesh) in einem Verhältnis von 40 g Harz pro 1 Serum gemischt, um den Wert der Natrium- und Kaliumionen (und gegebenenfalls anwesenden CaI-Citrated human blood serum was made by adding calcium ions and an- " final filtration defibrinated. Then, the obtained serum was coated with a polystyrene ion exchange resin having kerigebundsnen sulfonic acid groups ("Dowex 50" j 50-100 mesh) mixed in a ratio of 40 g resin per 1 serum, the value of the sodium and potassium ions (and any CaI
In dem Maße,In this scale,
ciumionen) im Serum zu verringern./wie die Wasserstoffionsn durch Austausch für Natrium- und Kaliumionen in das Serum freigesetzt werden, wird der pH-Wert des Serums mit einer wässrigen Lösung aus Lithiumhydroxyd auf einem Wert von etwa 6,2 + 0,2 gehalten oder eingestellt. Der Wert der Natriumionen wird durch diesen Ionenaustausch von etwa 165-205 Milliäquivalenten pro 1 Serum auf etwa ä 90-95 Milliäquivalente pro 1 Serum verringert. Der pH-Wert des endgültigen behandelten Serums wird untersuchtund mit Lithiumhydroxyd auf 6,2 + 0,2 eingestellt. Das rait Harz behandelte und in seinem pH-Wert eingestellte Serum wird lyophilisiert und dann mit "Freon TF" ( Trichlortrifluoräthan) durch gründliches Mischung von 75 g des getrockneten Serums mit 1500 ecm "Freon" extrahiert. Die Mischung wurde durch Whatman Nr. 1 Filterpapier filtriertcium ions) in the serum. / As the hydrogen ions are released into the serum by exchanging sodium and potassium ions, the pH of the serum is kept at a value of about 6.2 + 0.2 with an aqueous solution of lithium hydroxide or discontinued. The value of the sodium ions by this ion-exchange of about 165-205 milli-equivalents per 1 serum ä to about 90-95 milliequivalents per 1 serum reduced. The pH of the final treated serum is examined and adjusted to 6.2 + 0.2 with lithium hydroxide. The serum treated with resin and adjusted to its pH value is lyophilized and then extracted with "Freon TF" (trichlorotrifluoroethane) by thoroughly mixing 75 g of the dried serum with 1500 ecm "Freon". The mixture was filtered through Whatman No. 1 filter paper
209823/109 5209823/109 5
und der verbleibende Feststoff zum Trocknen ausgebreitet. Das trockene Material wurde dann mit dest. Wasser rekonstituiert und zur Entfernung von verbleibendem, fein zerteiltem Material filtriert. Dieses Produkt wurde als Konstrollstandard des flüssigen Grund-Blutseruma verwendet und auf die gswünschten Komponenten untersucht.and spread the remaining solid to dry. The dry material was then with dist. Water and reconstituted to remove any remaining finely divided material filtered. This product was used as the control standard of the liquid basic blood serum and adjusted as desired Components examined.
In diesem Beispiel wurden 3 Kontrollstandards mit den folgenden vorherbestiransten niedrigen, mittleren und hohen Konzentrationen hergestellt:In this example, 3 control standards were pre-determined with the following low, medium and high concentrations produced:
Komponente Kontrollstandardkonzentration·* Component Control standard concentration *
Natrium (Milliäquiv./l) Kalium (Milliäquiv./l) Calcium (mg3/.) Chlorid (Milliäquiv./l) BUN (mg^) Creatinin (mg^d) Harnsäure (mg0^) Glucose (mg°/>) Gesamtprotein (gtrf/o) Albumin (gn$>) CO2 (HCO3"") PBI (.Sodium (milliequiv. / L) Potassium (milliequiv. / L) Calcium (mg 3 /.) Chloride (milliequiv. / L) BUN (mg ^) Creatinine (mg ^ d) Uric acid (mg 0 ^) Glucose (mg ° / >) Total protein (gtrf / o) Albumin (gn $>) CO 2 (HCO 3 "") PBI (.
P (mg/o)P (mg / o)
* jede Konzentration liegt innerhalb von + 10 % des angegebenes Wertes* each concentration is within + 10% of the specified value
Zur Herstellung dieser drei Konzentrationsstärken wurde das oben hergestellt;» praktisch lipoproteinfreie getrocknete Serum in drei Teil geteilt und mit crsi unterschiedlichen Mengen an dest. Wasser rekonstituiert, wobei die unten angegebenen Proteinwerte als Grundlage verwendet wurden. Die rekonstituiert=:! Proben zeigten die folgende Analyse:To produce these three concentration strengths, the above was produced; practically lipoprotein-free dried serum divided into three parts and with crsi different amounts of dist. Reconstituted water, given below Protein values were used as a basis. The reconstituted = :! Samples showed the following analysis:
209823/1095209823/1095
Die rekonstituierten Proben 1,2 und 3 wurden durch Zugabe geeigneter Mengen der entsprechenden folgenden Materialien zur Herstellung der obigen Kontrollstandards mit niedriger, mittlerer und hoher Konzentration verwendetιThe reconstituted samples 1, 2 and 3 were made by adding appropriate amounts the appropriate following materials to prepare the above control standards used in low, medium and high concentration
zugefügtes Materialadded material
zugefügte Menge zu Probe added Me ng to e sample
0 2 3 / I U 9 S0 2 3 / I U 9 p
Die eingestellte Kontrollstandardmaterial wurde steril durch- einen "Millipore" Filter (0,22 Micron) filtriert und zur Verwendung als endgültige Konstrollstandards in Ampullen gegeben; die Standards sind den klinischen Laboratorien und anderen derartigen analytischen und Testlaboratorien zugänglich, die solche Blutserumkantrollstandards benötigen.The adjusted control standard material was sterilized by a "Millipore" Filter (0.22 micron) filtered and used as final control standards given in ampoules; the standards are available to clinical laboratories and other such analytical and test laboratories which do such Need blood serum control standards.
209823/ 1095209823/1095
Claims (8)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9253370A | 1970-11-24 | 1970-11-24 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2156604A1 true DE2156604A1 (en) | 1972-05-31 |
Family
ID=22233688
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19712156604 Pending DE2156604A1 (en) | 1970-11-24 | 1971-11-15 | Control standard for liquid blood serum |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US3682835A (en) |
| AU (1) | AU464164B2 (en) |
| BE (1) | BE775340A (en) |
| CA (1) | CA962193A (en) |
| CH (1) | CH542446A (en) |
| DE (1) | DE2156604A1 (en) |
| ES (1) | ES397245A1 (en) |
| FR (1) | FR2116164A5 (en) |
| GB (1) | GB1359232A (en) |
| IL (1) | IL38093A (en) |
| IT (1) | IT941771B (en) |
| LU (1) | LU64243A1 (en) |
| NL (1) | NL7116167A (en) |
| SE (1) | SE376309B (en) |
| ZA (1) | ZA717532B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0019939A1 (en) * | 1979-06-04 | 1980-12-10 | E.I. Du Pont De Nemours And Company | Serum and plasma clarification process |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3897363A (en) * | 1973-08-10 | 1975-07-29 | Baxter Laboratories Inc | Blood control standard |
| US3955925A (en) * | 1973-11-12 | 1976-05-11 | Proksch Gary J | Preparation of optically clear serum |
| US4190573A (en) * | 1974-02-14 | 1980-02-26 | Behringwerke Aktiengesellschaft | Process for the isolation of the polyvalent proteinase inhibitor |
| DE2461969A1 (en) * | 1974-12-31 | 1976-07-08 | Behringwerke Ag | STABLE BLOOD PLASMA, THE PROCESS FOR PRODUCING IT AND ITS USE AS A COMPARATIVE PLASMA IN COOLAGE EXAMINATIONS |
| US3958939A (en) * | 1975-01-08 | 1976-05-25 | Coulter Electronics, Inc. | Method for clarification of lipemic serum |
| US4011045A (en) * | 1975-02-14 | 1977-03-08 | Bonderman Dean P | Turbidity reduction in triglyceride standards |
| US4045176A (en) * | 1975-06-13 | 1977-08-30 | Proksch Gary J | Preparation of optically clear serum |
| US4007008A (en) * | 1975-07-30 | 1977-02-08 | Becker Milton J | Preparation of reference serum from animal blood |
| US4054488A (en) * | 1975-08-14 | 1977-10-18 | Marbach Edward P | Preservation of glucose in blood samples |
| US4116635A (en) * | 1977-03-14 | 1978-09-26 | Jaeger Mark A | General purpose in vitro anticoagulant |
| US4127502A (en) * | 1977-06-10 | 1978-11-28 | Eastman Kodak Company | Stabilizers for reconstituted, lyophilized samples |
| US4219440A (en) * | 1979-06-06 | 1980-08-26 | Coulter Electronics, Inc. | Multiple analysis hematology reference control reagent and method of making the same |
| US4158544A (en) * | 1978-07-17 | 1979-06-19 | Beckman Instruments, Inc. | Process for preparing a biological composition for use as a reference control in diagnostic analysis |
| US4324687A (en) * | 1979-02-15 | 1982-04-13 | Louderback Allan Lee | Blood biochemistry control standard |
| US4325832A (en) * | 1979-03-05 | 1982-04-20 | Beckman Instruments, Inc. | Enzyme reference composition |
| NL8500266A (en) * | 1985-01-31 | 1986-08-18 | Stichting Gastransport | CALIBRATION SOLUTION FOR ION-SELECTIVE ELECTRODES, DRY MATERIAL FOR MAKING IT OUT, METHOD FOR PREPARING THE SAME, AND USE THEREOF. |
| US4789545A (en) * | 1986-03-31 | 1988-12-06 | New York Blood Center, Inc. | Removal of lipid soluble process chemicals from biological materials by extraction with naturally occurring oils or synthetic substitutes thereof |
| US4956299A (en) * | 1986-12-31 | 1990-09-11 | Ciba Corning Diagnostics Corp. | Complement stabilization |
| US5028542A (en) * | 1990-02-07 | 1991-07-02 | Boehringer Mannheim Corporation | Glucose measurement control reagent and method of making the same |
| US6509192B1 (en) * | 1992-02-24 | 2003-01-21 | Coulter International Corp. | Quality control method |
| US6248869B1 (en) | 1997-05-29 | 2001-06-19 | Medical Analysis Systems, Inc. | Troponin I forms and use of the same |
| US20040137419A1 (en) * | 2003-01-15 | 2004-07-15 | V.I. Technologies, Inc. | Methods for removing microbicidal compounds from compositions |
| CN101930009B (en) * | 2009-11-19 | 2013-09-11 | 首都医科大学附属北京朝阳医院 | Serum calcium standard substance |
-
1970
- 1970-11-24 US US92533A patent/US3682835A/en not_active Expired - Lifetime
-
1971
- 1971-11-05 CA CA126,995A patent/CA962193A/en not_active Expired
- 1971-11-08 IL IL38093A patent/IL38093A/en unknown
- 1971-11-09 ZA ZA717532A patent/ZA717532B/en unknown
- 1971-11-10 AU AU35540/71A patent/AU464164B2/en not_active Expired
- 1971-11-10 GB GB5221371A patent/GB1359232A/en not_active Expired
- 1971-11-11 LU LU64243D patent/LU64243A1/xx unknown
- 1971-11-15 DE DE19712156604 patent/DE2156604A1/en active Pending
- 1971-11-16 BE BE775340A patent/BE775340A/en unknown
- 1971-11-18 CH CH1683971A patent/CH542446A/en not_active IP Right Cessation
- 1971-11-22 ES ES397245A patent/ES397245A1/en not_active Expired
- 1971-11-23 SE SE7114976A patent/SE376309B/xx unknown
- 1971-11-23 FR FR7142762A patent/FR2116164A5/fr not_active Expired
- 1971-11-23 IT IT31516/71A patent/IT941771B/en active
- 1971-11-24 NL NL7116167A patent/NL7116167A/xx unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0019939A1 (en) * | 1979-06-04 | 1980-12-10 | E.I. Du Pont De Nemours And Company | Serum and plasma clarification process |
Also Published As
| Publication number | Publication date |
|---|---|
| ES397245A1 (en) | 1975-03-01 |
| IL38093A0 (en) | 1972-01-27 |
| NL7116167A (en) | 1972-05-26 |
| CA962193A (en) | 1975-02-04 |
| FR2116164A5 (en) | 1972-07-07 |
| LU64243A1 (en) | 1972-06-02 |
| IT941771B (en) | 1973-03-10 |
| ZA717532B (en) | 1972-07-26 |
| IL38093A (en) | 1974-07-31 |
| GB1359232A (en) | 1974-07-10 |
| CH542446A (en) | 1973-09-30 |
| SE376309B (en) | 1975-05-12 |
| AU464164B2 (en) | 1975-08-21 |
| BE775340A (en) | 1972-03-16 |
| AU3554071A (en) | 1973-05-17 |
| US3682835A (en) | 1972-08-08 |
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