US3853476A - Diagnostic agent for the detection of bilirubin - Google Patents
Diagnostic agent for the detection of bilirubin Download PDFInfo
- Publication number
- US3853476A US3853476A US00382242A US38224273A US3853476A US 3853476 A US3853476 A US 3853476A US 00382242 A US00382242 A US 00382242A US 38224273 A US38224273 A US 38224273A US 3853476 A US3853476 A US 3853476A
- Authority
- US
- United States
- Prior art keywords
- test paper
- phosphoric acid
- carbon atoms
- ester
- bilirubin
- 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.)
- Expired - Lifetime
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- 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 title claims abstract description 83
- 238000001514 detection method Methods 0.000 title claims description 15
- 229940039227 diagnostic agent Drugs 0.000 title description 5
- 239000000032 diagnostic agent Substances 0.000 title description 5
- 238000012360 testing method Methods 0.000 claims abstract description 95
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract description 56
- -1 PHOSPHORIC ACID DIESTER Chemical class 0.000 claims abstract description 55
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims abstract description 43
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 41
- 239000012954 diazonium Substances 0.000 claims abstract description 25
- 150000001989 diazonium salts Chemical class 0.000 claims abstract description 24
- 239000002253 acid Substances 0.000 claims abstract description 18
- 210000001124 body fluid Anatomy 0.000 claims abstract description 13
- 239000010839 body fluid Substances 0.000 claims abstract description 13
- 238000005859 coupling reaction Methods 0.000 claims abstract description 12
- 230000008878 coupling Effects 0.000 claims abstract description 6
- 238000010168 coupling process Methods 0.000 claims abstract description 6
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 12
- 239000002250 absorbent Substances 0.000 claims description 11
- 230000002745 absorbent Effects 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 229920003002 synthetic resin Polymers 0.000 claims description 9
- 239000000057 synthetic resin Substances 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 125000005228 aryl sulfonate group Chemical group 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- ASMQGLCHMVWBQR-UHFFFAOYSA-N Diphenyl phosphate Chemical group C=1C=CC=CC=1OP(=O)(O)OC1=CC=CC=C1 ASMQGLCHMVWBQR-UHFFFAOYSA-N 0.000 claims description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 235000006408 oxalic acid Nutrition 0.000 claims description 5
- 239000003381 stabilizer Substances 0.000 claims description 5
- 239000000080 wetting agent Substances 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group 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 4
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- JTNCEQNHURODLX-UHFFFAOYSA-N 2-phenylethanimidamide Chemical compound NC(=N)CC1=CC=CC=C1 JTNCEQNHURODLX-UHFFFAOYSA-N 0.000 claims description 3
- MOMKYJPSVWEWPM-UHFFFAOYSA-N 4-(chloromethyl)-2-(4-methylphenyl)-1,3-thiazole Chemical compound C1=CC(C)=CC=C1C1=NC(CCl)=CS1 MOMKYJPSVWEWPM-UHFFFAOYSA-N 0.000 claims description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 3
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 3
- 229910000343 potassium bisulfate Inorganic materials 0.000 claims description 3
- 235000019983 sodium metaphosphate Nutrition 0.000 claims description 3
- HDFFVHSMHLDSLO-UHFFFAOYSA-N Dibenzyl phosphate Chemical group C=1C=CC=CC=1COP(=O)(O)OCC1=CC=CC=C1 HDFFVHSMHLDSLO-UHFFFAOYSA-N 0.000 claims description 2
- XTCDRDNDDHPDJE-UHFFFAOYSA-N bis(3,5-dimethylphenyl) hydrogen phosphate Chemical group CC1=CC(C)=CC(OP(O)(=O)OC=2C=C(C)C=C(C)C=2)=C1 XTCDRDNDDHPDJE-UHFFFAOYSA-N 0.000 claims description 2
- PLUDEAUQZKPAIN-UHFFFAOYSA-N bis(4-methylphenyl) hydrogen phosphate Chemical group C1=CC(C)=CC=C1OP(O)(=O)OC1=CC=C(C)C=C1 PLUDEAUQZKPAIN-UHFFFAOYSA-N 0.000 claims description 2
- YQHVEGTZGGQQMV-UHFFFAOYSA-N dicyclohexyl hydrogen phosphate Chemical group C1CCCCC1OP(=O)(O)OC1CCCCC1 YQHVEGTZGGQQMV-UHFFFAOYSA-N 0.000 claims description 2
- WJZUIWBZDGBLKK-UHFFFAOYSA-N dipentyl hydrogen phosphate Chemical group CCCCCOP(O)(=O)OCCCCC WJZUIWBZDGBLKK-UHFFFAOYSA-N 0.000 claims description 2
- 239000003463 adsorbent Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 7
- 125000001931 aliphatic group Chemical group 0.000 abstract description 5
- 150000003839 salts Chemical class 0.000 abstract description 4
- 238000006243 chemical reaction Methods 0.000 description 14
- 210000002700 urine Anatomy 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 230000035945 sensitivity Effects 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- ZYECOAILUNWEAL-NUDFZHEQSA-N (4z)-4-[[2-methoxy-5-(phenylcarbamoyl)phenyl]hydrazinylidene]-n-(3-nitrophenyl)-3-oxonaphthalene-2-carboxamide Chemical group COC1=CC=C(C(=O)NC=2C=CC=CC=2)C=C1N\N=C(C1=CC=CC=C1C=1)/C(=O)C=1C(=O)NC1=CC=CC([N+]([O-])=O)=C1 ZYECOAILUNWEAL-NUDFZHEQSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 238000007598 dipping method Methods 0.000 description 4
- 238000005470 impregnation Methods 0.000 description 4
- 206010023126 Jaundice Diseases 0.000 description 3
- 244000172533 Viola sororia Species 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 150000005690 diesters Chemical class 0.000 description 3
- QLZHNIAADXEJJP-UHFFFAOYSA-N Phenylphosphonic acid Chemical compound OP(O)(=O)C1=CC=CC=C1 QLZHNIAADXEJJP-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 125000000664 diazo group Chemical class [N-]=[N+]=[*] 0.000 description 2
- 210000000232 gallbladder Anatomy 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- XZZNDPSIHUTMOC-UHFFFAOYSA-N triphenyl phosphate Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)(=O)OC1=CC=CC=C1 XZZNDPSIHUTMOC-UHFFFAOYSA-N 0.000 description 2
- OBHRVMZSZIDDEK-UHFFFAOYSA-N urobilinogen Chemical compound CCC1=C(C)C(=O)NC1CC1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(CC3C(=C(CC)C(=O)N3)C)N2)CCC(O)=O)N1 OBHRVMZSZIDDEK-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- FRASJONUBLZVQX-UHFFFAOYSA-N 1,4-naphthoquinone Chemical compound C1=CC=C2C(=O)C=CC(=O)C2=C1 FRASJONUBLZVQX-UHFFFAOYSA-N 0.000 description 1
- GKQHIYSTBXDYNQ-UHFFFAOYSA-M 1-dodecylpyridin-1-ium;chloride Chemical compound [Cl-].CCCCCCCCCCCC[N+]1=CC=CC=C1 GKQHIYSTBXDYNQ-UHFFFAOYSA-M 0.000 description 1
- RUFPHBVGCFYCNW-UHFFFAOYSA-N 1-naphthylamine Chemical compound C1=CC=C2C(N)=CC=CC2=C1 RUFPHBVGCFYCNW-UHFFFAOYSA-N 0.000 description 1
- DALFRMLWFWYVJL-UHFFFAOYSA-N 2,4,6-trichlorobenzenediazonium Chemical class ClC1=CC(Cl)=C([N+]#N)C(Cl)=C1 DALFRMLWFWYVJL-UHFFFAOYSA-N 0.000 description 1
- LNZODIBYVPYDSG-UHFFFAOYSA-N 2,6-dibromobenzenediazonium Chemical compound BrC1=CC=CC(Br)=C1[N+]#N LNZODIBYVPYDSG-UHFFFAOYSA-N 0.000 description 1
- HGOUHLGJFUPVGS-UHFFFAOYSA-N 2-chlorobenzenediazonium Chemical compound ClC1=CC=CC=C1[N+]#N HGOUHLGJFUPVGS-UHFFFAOYSA-N 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- ICMFHHGKLRTCBM-UHFFFAOYSA-N 4-nitrobenzenediazonium Chemical class [O-][N+](=O)C1=CC=C([N+]#N)C=C1 ICMFHHGKLRTCBM-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 241001662043 Icterus Species 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- 206010067125 Liver injury Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 235000005811 Viola adunca Nutrition 0.000 description 1
- 240000009038 Viola odorata Species 0.000 description 1
- 235000013487 Viola odorata Nutrition 0.000 description 1
- 235000002254 Viola papilionacea Nutrition 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- CIZVQWNPBGYCGK-UHFFFAOYSA-N benzenediazonium Chemical class N#[N+]C1=CC=CC=C1 CIZVQWNPBGYCGK-UHFFFAOYSA-N 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- HFACYLZERDEVSX-UHFFFAOYSA-N benzidine Chemical class C1=CC(N)=CC=C1C1=CC=C(N)C=C1 HFACYLZERDEVSX-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- YRIUSKIDOIARQF-UHFFFAOYSA-N dodecyl benzenesulfonate Chemical compound CCCCCCCCCCCCOS(=O)(=O)C1=CC=CC=C1 YRIUSKIDOIARQF-UHFFFAOYSA-N 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940071161 dodecylbenzenesulfonate Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- BUBWTSJXUHKBBX-UHFFFAOYSA-N ethyl acetate;sodium Chemical compound [Na].CCOC(C)=O BUBWTSJXUHKBBX-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 208000020694 gallbladder disease Diseases 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 231100000234 hepatic damage Toxicity 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000008818 liver damage Effects 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000002560 nitrile group Chemical group 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- CMPQUABWPXYYSH-UHFFFAOYSA-N phenyl phosphate Chemical compound OP(O)(=O)OC1=CC=CC=C1 CMPQUABWPXYYSH-UHFFFAOYSA-N 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 238000011896 sensitive detection Methods 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000012209 synthetic fiber Substances 0.000 description 1
- 229920002994 synthetic fiber Polymers 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 125000005023 xylyl group Chemical group 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
- G01N33/72—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood pigments, e.g. haemoglobin, bilirubin or other porphyrins; involving occult blood
- G01N33/728—Bilirubin; including biliverdin
-
- 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
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/903—Diazo reactions
-
- 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
- Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
- Y10T436/145555—Hetero-N
- Y10T436/146666—Bile pigment
Definitions
- cycloaliphatic araliphatic or aromatic radicals and contain not more than 18 carbon atoms each.
- bilirubin occurs in the urine in the early stages, even before the bilirubin content of the serum increases and clinical signs of jaundice appear.
- this type of jaundice can be distinguished from the socalled haemolytic icterus in which an increased bilirubin level can only be detected in the serum but not in the urine.
- German Patent No. 1,102,444 there is described a reagent tablet containing a diazonium salt and a strong acid which is placed on a spot plate moistened with the body fluid to be tested and, after moistening with water, makes the bilirubin visible as a violet ring on the substrate.
- test papers these are absorbent carriers which have been impregnated with all the reagents necessary for the detection reaction.
- R and R which may be the same or different, are
- the substituents R and R are preferably identical because phosphoric acid diesters of this type are especially easy to prepare.
- the aliphatic radicals R and R can be straight-chained or branched and can contain up to 18 carbon atoms, the effectiveness of the esters initially increasing with the increasing number of carbon atoms and, finally, above a chain length of about 14 carbon atoms, due to the increasingly hydrophobic nature of the esters, again decreases.
- cycloalkyl radicals those containing five to eight carbon atoms have proved to be preferable.
- substituents for the aliphatic and cycloaliphatic radicals include halogen atoms, preferably chlorine or bromine atoms, nitro groups and alkoxy radicals containing up to 8 carbon atoms.
- R, and R are aromatic radicals.
- aromatic radicals there are preferably used monoor polynuclear, unsubstituted or substituted aryl radicals, for example, phenyl, xylyl, tolyl, chlorophenyl, nitrophenyl or naphthyl radicals.
- araliphatic radicals include the phenyl and naphthyl radicals connected to the phosphoric acid residue via an alkylene bridge containing up to three carbon atoms.
- the present invention provides test papers for the detection of bilirubin in body fluids which contain a diazonium salt capable of coupling with bilirubin and an amount of an acid which is sufficient for the coupling reaction, as well as a phosphoric acid diester of general formula (I).
- the phosphoric acid diesters of general formula (I) are known (see Methoden d. Org. Chem., Houben- Weyl, Vol. XII/2, pp 226 et seq.).
- the phosphoric acid diesters of general formula (I) exert their sensitivity-increasing and reactionpromoting action even at concentrations of 2-3 percent in the solution used for impregnating the test papers; only the lower alkyl esters require a somewhat higher concentration. For this reason, the phosphoric acid diesters of general formula (I) usually cannot replace the acid component needed for the coupling reaction so that, for the maintenance of a strongly acidic pH value, additional amounts of acid are necessary. For this purpose, a large number of acids can be used. Those which have proved to be especially useful include oxalic acid, citric acid, potassium bisulfate and, especially with regard to the stability of the diazonium salt, commercially available metaphosphoric acid, which can contain up to about 60 percent of its sodium salt.
- Test papers which, in addition to the diazonium salts, only contain these acids and no diesters (l) react substantially more slowly with bilirubin and have an insufficient sensitivity for an accurate determination of bilirubin. It is still completely unknown upon what this action of the diesters (I) used according to the present invention depends since there is absolutely no chemical similarity with the accelerators of the diazo reaction otherwise used, for example caffeine or sodium benzoate.
- diesters of phosphoric acid of general formula (I), used according to the present invention are effective.
- the good effect of these phosphoric acid diesters (l) is in complete contrast to the complete ineffectiveness of phosphoric acid, phosphoric acid monoesters, benzenephosphonic acid and phosphoric acid triphenyl ester.
- test papers are intended for the determination of bilirubin in the serum or in urine, i.e. the formulation of the test strips must be appropriately modified.
- diazonium salts which, from the chemical standpoint, can be expected to give a rapid and sensitive reaction.
- diazonium salts which exclusively or preponderantly contain electron-attracting groups.
- the substituents can be nitro groups, halogen atoms, carboxyl groups, sulfonic acid residues, nitrile groups or quaternary ammonium groups.
- electron-donating groups for example alkoxy radicals, can also be present.
- diazotized naphthylamine and benzidine derivatives can also be used.
- benzene-diazonium salts which exclusively contain electron-donating groups, such as alkoxy, alkyl or arylamino radicals, because these only react comparatively slowly with bilirubin.
- the reaction color is red-violet to blue-green and, in addition, as has been found from experience, with increasing acidity of the phosphoric acid diesters, the colors are bathochromically displaced.
- 3-nitroand 2,4,6-trichlorobenzene-diazonium salts are preferably used.
- the diazonium salts are preferably used in the form of fluoborates since the stability thereof is well-known; however, other stable salts, for example, arylsulfonates, especially naphthalene-1,S-disulfonates, can also be employed.
- the diazonium salts can be used in the impregnation solutions in amounts of from 0.02 to about 2 percent and preferably of 0.05 to 0.5 percent.
- reagents for the detection of bilirubin in the urine there can be used, for example, 2,6-dihalobenzenediazonium salts, especially the 2,6-dichloro and/or -dibromo derivatives, since these only possess the abovementioned disadvantages to a minor extent.
- the salts there can be used the conventional stabilizing anions, for example, the fluoborates and aryl-sulfonates.
- Test papers are obtained which, depending upon the bilirubin concentration of the urine, change from yellow via orange to red-violet.
- the concentration of the diazonium salts in the impregnation solutions can be between 0.02 and 0.5 percent and preferably between 0.05 and 0.15 percent.
- the test papers for urine bilirubin can, of course, also be used for serum bilirubin.
- the bilirubin test papers according to the present invention for serum and urine preferably contain stabilizing agents for the diazonium salts, for example, sodium fluoborate, magnesium sulfate, sodium metaphosphate, aryl-sulfonates or the like.
- wetting agents in order to improve the absorptive powers of the test papers.
- wetting agents which are still surface-active in the strongly acidic medium formed after dipping into the body fluid, namely, cationic agents (for example lauryl-pyridinium chloride), non-ionic agents (for example, polyoxyethylene triglyceride) and anionic agents, especially sulfates and sulfonates (for example, dodecyl-benzene-sulfonate).
- the wetting agents can be used in the impregnation solutions in concentrations of 0. l to 2 percent and preferably of 0.2 to 0.5 percent.
- an absorbent paper can first be impregnated with a mixture of a diazonium salt and an acid, for example metaphosphoric acid in an aqueous medium and then impregnated with an ester (l), for example phosphoric acid diphenyl ester, in ethyl acetate or chloroform.
- an acid for example metaphosphoric acid in an aqueous medium
- an ester for example phosphoric acid diphenyl ester
- absorbent carrier it is preferred to use filter paper but other absorbent carriers, for example, glass fiber paper or synthetic fiber fabrics and fleeces made from acid resistant fibers, such as polyesters and polypropylene, can also be used.
- acid resistant fibers such as polyesters and polypropylene
- test paper is to be understood to include all of these materials.
- test papers can be cut up into long strips and rolled up and, when needed, it is only necessary to cut or tear off a small piece. They can also be cut up into small rectangular pieces and stuck or sealed on to the lower end of narrow synthetic resin strips. It is especially advantageous when the test papers are sealed between two synthetic resin foils in the manner described in German Pat. No. 1,546,307 or between a synthetic resin film and a meshwork in the manner described in German Pat. No. 2,118,455 because there is then no danger that the reagents might be washed out upon dipping into a body fluid.
- Test papers which contain 2,6-dibromobenzenediazonium fluoborate reacted in an analogous manner.
- Test papers of otherwise the same composition but which did not contain the phosphoric acid diphenyl ester required 2-5 minutes for the reaction and had a limit of sensitivity of about I to 2 mg.%. This also applied to test papers which, instead of phosphoric acid diphenyl ester, contained phosphoric acid monophenyl ester, phosphoric acid triphenyl ester or benzenephosphonic acid.
- EXAMPLE 2 EXAMPLE 3 Filter paper was impregnated with the following solutions and then dried at 40C.:
- Test paper for the detection of bilirubin in body fluids comprising an absorbent carrier and, impregnated thereinto a diazonium salt capable of coupling with bilirubin, an amount of an acid which is sufficient for the coupling reaction, and at least one phosphoric acid diester of the general formula:
- R and R are individually selected from unsubstituted or substituted aliphatic, cycloaliphatic, araliphatic or aromatic radicals, and contain not more than 18 carbon atoms each.
- Test paper as claimed in claim 26, wherein the stabilizing agent is sodium fluoborate. magnesium sulfate, sodium metaphosphate or an aryl-sulfonate.
- Test paper as claimed in claim 1 also containing a wetting agent.
- Method for detecting bilirubin in body fluids which method comprises contacting a test sample suspected of containing bilirubin with a test strip as claimed in claim 1.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Urology & Nephrology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2240357A DE2240357C2 (de) | 1972-08-17 | 1972-08-17 | Testpapier zum Nachweis von Bilirubin in Körperflüssigkeiten |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3853476A true US3853476A (en) | 1974-12-10 |
Family
ID=5853744
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US00382242A Expired - Lifetime US3853476A (en) | 1972-08-17 | 1973-07-24 | Diagnostic agent for the detection of bilirubin |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US3853476A (de) |
| JP (1) | JPS5328119B2 (de) |
| AT (1) | AT327399B (de) |
| BE (1) | BE863862Q (de) |
| CH (1) | CH572212A5 (de) |
| DE (1) | DE2240357C2 (de) |
| FR (1) | FR2199888A5 (de) |
| GB (1) | GB1389366A (de) |
| HK (1) | HK16278A (de) |
| KE (1) | KE2829A (de) |
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3915649A (en) * | 1974-08-14 | 1975-10-28 | American Cyanamid Co | Bilirubin test material |
| US3980696A (en) * | 1974-07-25 | 1976-09-14 | Beckman Instruments, Inc. | Photodosimeter film badge |
| US4069017A (en) * | 1977-01-14 | 1978-01-17 | Eastman Kodak Company | Colorimetric assay for bilirubin |
| US4115064A (en) * | 1977-02-07 | 1978-09-19 | Pierce Chemical Company | Method for bilirubin determination |
| US4161507A (en) * | 1977-06-23 | 1979-07-17 | Behringwerke Aktiengesellschaft | Stabilized diagnostic test strip for the detection of urobilinogen |
| US4246133A (en) * | 1979-06-22 | 1981-01-20 | Sherwood Medical Industries Inc. | Stabilized diazotized sulfanilic acid solutions |
| US4382062A (en) * | 1980-06-06 | 1983-05-03 | Behringwerke Aktiengesellschaft | Test agent for the detection of coupling compounds, and a process for its preparation |
| US5955374A (en) * | 1994-11-23 | 1999-09-21 | Smith; Jack V. | Method of detection of bilirubin in urine on an automated analyzer |
| US7846383B2 (en) | 2006-12-15 | 2010-12-07 | Kimberly-Clark Worldwide, Inc. | Lateral flow assay device and absorbent article containing same |
| US8012761B2 (en) | 2006-12-14 | 2011-09-06 | Kimberly-Clark Worldwide, Inc. | Detection of formaldehyde in urine samples |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2555276B2 (ja) * | 1994-09-07 | 1996-11-20 | 古河電気工業株式会社 | 平面状光ファイバユニット |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2854317A (en) * | 1950-08-08 | 1958-09-30 | Miles Lab | Method and composition for testing bilirubin in urine |
| US3511607A (en) * | 1967-10-06 | 1970-05-12 | Smithkline Corp | Laboratory reagent for assay of total bilirubin |
| US3585004A (en) * | 1969-03-21 | 1971-06-15 | Miles Lab | Test composition and device for detecting couplable compounds |
| US3585001A (en) * | 1969-02-17 | 1971-06-15 | Miles Lab | Stabilized test device and process for detecting couplable compounds |
| US3652222A (en) * | 1969-04-07 | 1972-03-28 | American Monitor Corp | Bilirubin assay |
| US3754862A (en) * | 1971-03-05 | 1973-08-28 | Boehringer Mannheim Gmbh | Reagnet composition and method for determining total bilirubin |
-
1972
- 1972-08-17 DE DE2240357A patent/DE2240357C2/de not_active Expired
-
1973
- 1973-07-24 US US00382242A patent/US3853476A/en not_active Expired - Lifetime
- 1973-08-14 CH CH1170173A patent/CH572212A5/xx not_active IP Right Cessation
- 1973-08-14 GB GB3842973A patent/GB1389366A/en not_active Expired
- 1973-08-14 FR FR7329672A patent/FR2199888A5/fr not_active Expired
- 1973-08-16 AT AT715373A patent/AT327399B/de not_active IP Right Cessation
- 1973-08-17 JP JP9233073A patent/JPS5328119B2/ja not_active Expired
-
1978
- 1978-02-10 BE BE185079A patent/BE863862Q/xx not_active IP Right Cessation
- 1978-03-14 KE KE2829A patent/KE2829A/xx unknown
- 1978-03-23 HK HK162/78A patent/HK16278A/xx unknown
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2854317A (en) * | 1950-08-08 | 1958-09-30 | Miles Lab | Method and composition for testing bilirubin in urine |
| US3511607A (en) * | 1967-10-06 | 1970-05-12 | Smithkline Corp | Laboratory reagent for assay of total bilirubin |
| US3585001A (en) * | 1969-02-17 | 1971-06-15 | Miles Lab | Stabilized test device and process for detecting couplable compounds |
| US3585004A (en) * | 1969-03-21 | 1971-06-15 | Miles Lab | Test composition and device for detecting couplable compounds |
| US3652222A (en) * | 1969-04-07 | 1972-03-28 | American Monitor Corp | Bilirubin assay |
| US3754862A (en) * | 1971-03-05 | 1973-08-28 | Boehringer Mannheim Gmbh | Reagnet composition and method for determining total bilirubin |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3980696A (en) * | 1974-07-25 | 1976-09-14 | Beckman Instruments, Inc. | Photodosimeter film badge |
| US4062713A (en) * | 1974-07-25 | 1977-12-13 | Beckman Instruments, Inc. | Photodosimeter film badge |
| US3915649A (en) * | 1974-08-14 | 1975-10-28 | American Cyanamid Co | Bilirubin test material |
| US4069017A (en) * | 1977-01-14 | 1978-01-17 | Eastman Kodak Company | Colorimetric assay for bilirubin |
| US4115064A (en) * | 1977-02-07 | 1978-09-19 | Pierce Chemical Company | Method for bilirubin determination |
| US4161507A (en) * | 1977-06-23 | 1979-07-17 | Behringwerke Aktiengesellschaft | Stabilized diagnostic test strip for the detection of urobilinogen |
| US4246133A (en) * | 1979-06-22 | 1981-01-20 | Sherwood Medical Industries Inc. | Stabilized diazotized sulfanilic acid solutions |
| US4382062A (en) * | 1980-06-06 | 1983-05-03 | Behringwerke Aktiengesellschaft | Test agent for the detection of coupling compounds, and a process for its preparation |
| US5955374A (en) * | 1994-11-23 | 1999-09-21 | Smith; Jack V. | Method of detection of bilirubin in urine on an automated analyzer |
| US8012761B2 (en) | 2006-12-14 | 2011-09-06 | Kimberly-Clark Worldwide, Inc. | Detection of formaldehyde in urine samples |
| US7846383B2 (en) | 2006-12-15 | 2010-12-07 | Kimberly-Clark Worldwide, Inc. | Lateral flow assay device and absorbent article containing same |
Also Published As
| Publication number | Publication date |
|---|---|
| DE2240357B1 (de) | 1974-02-14 |
| CH572212A5 (de) | 1976-01-30 |
| JPS5328119B2 (de) | 1978-08-12 |
| ATA715373A (de) | 1975-04-15 |
| BE863862Q (fr) | 1978-08-10 |
| HK16278A (en) | 1978-03-31 |
| FR2199888A5 (de) | 1974-04-12 |
| DE2240357A1 (de) | 1974-02-14 |
| JPS4965887A (de) | 1974-06-26 |
| AT327399B (de) | 1976-01-26 |
| GB1389366A (en) | 1975-04-03 |
| KE2829A (en) | 1978-04-07 |
| DE2240357C2 (de) | 1974-09-12 |
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