US3645691A - Method of quantitatively determining iodine and thyroid hormones - Google Patents

Method of quantitatively determining iodine and thyroid hormones Download PDF

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Publication number
US3645691A
US3645691A US802421A US3645691DA US3645691A US 3645691 A US3645691 A US 3645691A US 802421 A US802421 A US 802421A US 3645691D A US3645691D A US 3645691DA US 3645691 A US3645691 A US 3645691A
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reaction
iodine
cerium
nitric acid
thyroid hormones
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US802421A
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Guenter Knapp
Hans Spitzy
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    • 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
    • G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
    • G01N33/78—Thyroid gland hormones, e.g. T3, T4, TBH, TBG or their receptors
    • 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
    • Y10T436/19—Halogen containing

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  • ABSTRACT Improved method of quantitatively determining iodine or thyroid hormones according to the method of Sandell and Kolthoff by replacing sulfuric acid by nitric acid.
  • a preferred measuring apparatus consists of a thermostat, a photometer, and an evaluating and plotting instrument.
  • Iodine or, respectively, thyroid hormones have a catalytic effect upon the course of reaction I, i.e., the more iodine or thyroid hormones are present in the preparation to be analyzed, the more rapidly proceeds said reaction I.
  • the speed of reaction is proportional to the iodine concentration or, respectively, to the thyroid hormone concentration. In this manner it is possible to determine iodine or, respectively, thyroid hormones even in the nanogram range.
  • This known analytical method is carried out in the following manner:
  • a predetermined amount of a solution of arsenous oxide Asp, in concentrated sulfuric acid is added to the test solution and the temperature of the mixture is adjusted to reaction temperature, i.e., usually to a temperature between 20 C. and 60 C.
  • a predetermined amount of a cerium (IV) sulfate solution in sulfuric acid is added thereto.
  • the mixture is allowed to react at the predetermined temperature for a definite period of time.
  • Said reaction time is selected in accordance with the order of magnitude of the amount of iodine to be determined and with the respective selected reaction temperature.
  • the reaction time is usually between minutes and 40 minutes. Thereafter, the content of the test solution of cerium (IV) ions is determined photometrically.
  • Another object of the present invention is to provide a simple and effective apparatus for carrying out said novel method.
  • the method according to the present invention is characterized by using nitric acid, in place of sulfuric acid as used heretofore, for acidifying the reaction mixture, i.e., the test solution, the arsenous acid solution, and the cerium (IV) compound solution. It is of importance to add nitric acid in an amount sufficient to produce a reaction mixture containing at least 6 percent, by weight, of nitric acid and preferably between about 12 percent and about 30 percent, by weight, of nitric acid in order to achieve satisfactory and accurate results. This change in composition of the reaction mixture increases the sensitivity of the reaction about twentyfold.
  • the novel process according to the present invention is based upon these and the following fundamentally changed reaction conditions. While heretofore the iodine-containing test solution was mixed with the arsenous acid and the mixture was brought to reaction temperature in a thermostat, whereafter the reaction was initiated by the addition of the cerium (IV) compound solution, all the components of the reaction mixture, i.e., iodine-containing test solution, arsenous acid, nitric acid, and cerium (IV) compound solution, are mixed and all together are brought to reaction temperature when proceeding according to the present invention.
  • the iodine-containing test solution was mixed with the arsenous acid and the mixture was brought to reaction temperature in a thermostat, whereafter the reaction was initiated by the addition of the cerium (IV) compound solution
  • all the components of the reaction mixture i.e., iodine-containing test solution, arsenous acid, nitric acid, and cerium (IV) compound solution, are mixed and all together are brought to reaction temperature when proceeding according to the
  • the measuring technique used in the method according to this invention also differs essentially from the measuring technique of the known methods.
  • the content of cerium (IV) ions and thus the iodine content of the test solution was determined only after termination of the reaction.
  • the speed of reaction I is directly determined when proceeding according to the present invention. This result is achieved by continuously measuring the decrease in cerium (IV) ion concentration in the reaction mixture.
  • Reaction I proceeds normally as a reactiori of the first order as expressed by the following equation II:
  • Quantitative determination of iodine or, respectively, of thyroid hormones by the method of this invention is preferably carried out in a measuring apparatus which takes into account the specific requirements of the novel method.
  • Such a measuring apparatus comprises a thermostat, a photometer, and an evaluation and plotting instrument.
  • the feedpipe supplying the reaction mixture to the cuvette of the photometer passes through the thermostat preferably in coiled form.
  • the evaluation and plotting instrument attached to the photometer transforms the transmission values observed in the photometer into the Iogarithmus of extinction and records the reaction curve log Ext-time. Said double logarithmic transformation of the transmission values into the logarithmus of extinction can be carried out electromechanically by means of a cam disk or fully electronically.
  • FIG. 1 illustrates schematically the manner in which the method according to this invention is'carried out in such a preferred apparatus.
  • FIG. 2 illustrates schematically a preferred evaluation and plotting instrument.
  • FIG. 3 which includes FIGS. 3a to 3d, illustrates calibration or standardization curves at different temperatures and increasing nitric acid content as they are used for comparison with the samples to be tested;
  • FIG. 4 shows a curve illustrating the increase in sensitivity depending uponthe nitric acid concentration.
  • the test solution of which the iodine content or, respectively, the content of thyroid hormones is to be determined is placed in flask 1.
  • Arsenous acid which preferably is prepared by dissolving arsenous oxide A5 in sodium hydroxide solution and weakly acidifying said solution with sulfuric acid, nitric acid, and a cerium (IV) compound solution are added thereto and are intimately mixed therewith as indicated in FIG. 1.
  • the amount of nitric acid to be added must be sufficient to yield a test mixture containing at least 6.0 percent of nitric acid. Any cerium (IV) compound may be used in this test.
  • ammonium cerium (IV) nitrate ammonium cerium (IV) sulfate, and cerium (IV) sulfate.
  • the resulting reaction mixture is introduced by suction by means of pump 7 (not shown) through pipe line 2 into flow-through thermostat 3 whereby it attains the desired reaction temperature within a few seconds. Thereafter, the mixture passes into flowthrough cuvette 6 of photometer which is also kept at reaction temperature. As soon as the cuvette 6 is completely filled with the reaction mixture, pump 7 is disconnected and the measuring operation starts. Due to the reaction according to reaction equation I given hereinabove, the yellow cerium (IV) ions disappear because they are converted into the colorless cerium (III) ions.
  • test and reactant solutions may be mixed at the desired reaction temperature.
  • the preferred procedure is to first mix said solutions and then to adjust the temperature of the reaction mixture in the thermostat to the desired reaction temperature.
  • FIG. 2 shows schematically a preferred compensating recording apparatus, the compensating potentiometer ll of which is driven by a servomotor 14 by means of cam disk 13 and rack 12 cooperating with the pinion of the compensating potentiometer 11.
  • the recording instrument is provided with a trailing or drag pen which is dragged or pulled along from the zero point at the start of the measurement independently from the light transmission value of the reaction solution.
  • the recorder is firmly connected with the photometer 5 and the pen can be engaged at any given time during the reaction. From the moment of its engagement the pen records the straight line representing the course of the reaction for exactly 1 minute. It is then disengaged and is returned to the zero point.
  • the recorded height of the peak i.e., the greatest distance of the pen from the zero line is proportional to the gradient of the straight line representing the course of the reaction and thus is proportional to the iodine concentration or, respectively, the thyroid hormone concentration.
  • the testing and measuring system according to the present invention has the great advantage that measurement may be started at any time in the course of the reaction because the gradient of the straight line representing the course of the'reaction is always of the same inclination independently from the start of the reaction and at any period of time within the measuring range.
  • Thermostat 3, photometer 5, and electronic evaluation and plotting instrument 10 (FIG. 1) as well as the compensating recording apparatus may be conventional instruments.
  • FIGS. 3a to 3d show standardization curves recorded with standard solutions of known iodine content. It is evident therefrom that the sensitivity of the reaction which is expressed by the gradient or rate of increase of the standard curve or straight line, increases with increasing temperature and increasing nitric acid content. The peaks of said curves or straight lines are proportional to the iodineconcentration.
  • a suitable photometer 5 which has proved of value is the spectrophotometer of the firm Carl Zeiss. It is provided with a cuvette holder and a l-cm. flowthrough cuvette 5. The thermostat coil 3 is arranged within the inflow of said cuvette 5. The outlet of the cuvette is connected via a shutoff valve to a water jet pump. As stated above, however, any type ofspectrophotometer may be used for carrying out the method according to the present invention.
  • FIG. 4 represents a diagram which shows that the sensitivity of the reaction is dependent on the nitric acid concentration of the reaction mixture.
  • the curve illustrates the coefficient of sensitivity increase. It is evident from the curve that at least a normal nitric acid concentration is required to produce satisfactory results and that best results are achieved starting with 2N concentration.
  • cerium (IV) compound should be sufficient to produce a reaction mixture the light transmissivity of which. is at the starting point of the photometer scale, i.e., at about 5 percent to 10 percent transmissivity, at the start of the reaction.
  • step (a) the reactants are admixed in step (a) to the test solution in the order arsenous acid, nitric acid, and cerium (lV) compound solution.
  • test solution is first mixed with arsenous acid, nitric acid, and cerium (lV) compound solution whereafter the reaction mixture is adjusted to the constant reaction temperature.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • Endocrinology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
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US802421A 1968-02-27 1969-02-26 Method of quantitatively determining iodine and thyroid hormones Expired - Lifetime US3645691A (en)

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Application Number Priority Date Filing Date Title
AT188968A AT277936B (de) 1968-02-27 1968-02-27 Verfahren zur quantitativen Bestimmung von Jod und von Schilddrüsenhormonen sowie Vorrichtung zur Durchführung des Verfahrens

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Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3874794A (en) * 1972-04-21 1975-04-01 Bodenseewerk Perkin Elmer Co Method and apparatus for photometric analysis of substantially colorless components of sample
WO2011143361A2 (en) 2010-05-11 2011-11-17 Veracyte, Inc. Methods and compositions for diagnosing conditions
WO2014151764A2 (en) 2013-03-15 2014-09-25 Veracyte, Inc. Methods and compositions for classification of samples
EP3029158A1 (de) 2008-11-17 2016-06-08 Veracyte, Inc. Verfahren und zusammensetzungen zur molekularen profilerstellung für die diagnose von erkrankungen
US9856537B2 (en) 2009-12-09 2018-01-02 Veracyte, Inc. Algorithms for disease diagnostics
EP3360978A2 (de) 2009-05-07 2018-08-15 Veracyte, Inc. Verfahren zur diagnose von schilddrüsenerkrankungen
US10114924B2 (en) 2008-11-17 2018-10-30 Veracyte, Inc. Methods for processing or analyzing sample of thyroid tissue
US10407731B2 (en) 2008-05-30 2019-09-10 Mayo Foundation For Medical Education And Research Biomarker panels for predicting prostate cancer outcomes
US10422009B2 (en) 2009-03-04 2019-09-24 Genomedx Biosciences Inc. Compositions and methods for classifying thyroid nodule disease
US10446272B2 (en) 2009-12-09 2019-10-15 Veracyte, Inc. Methods and compositions for classification of samples
US10494677B2 (en) 2006-11-02 2019-12-03 Mayo Foundation For Medical Education And Research Predicting cancer outcome
US10513737B2 (en) 2011-12-13 2019-12-24 Decipher Biosciences, Inc. Cancer diagnostics using non-coding transcripts
US10865452B2 (en) 2008-05-28 2020-12-15 Decipher Biosciences, Inc. Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer
US11035005B2 (en) 2012-08-16 2021-06-15 Decipher Biosciences, Inc. Cancer diagnostics using biomarkers
US11078542B2 (en) 2017-05-12 2021-08-03 Decipher Biosciences, Inc. Genetic signatures to predict prostate cancer metastasis and identify tumor aggressiveness
US11208697B2 (en) 2017-01-20 2021-12-28 Decipher Biosciences, Inc. Molecular subtyping, prognosis, and treatment of bladder cancer
US11217329B1 (en) 2017-06-23 2022-01-04 Veracyte, Inc. Methods and systems for determining biological sample integrity
US11414708B2 (en) 2016-08-24 2022-08-16 Decipher Biosciences, Inc. Use of genomic signatures to predict responsiveness of patients with prostate cancer to post-operative radiation therapy
US11639527B2 (en) 2014-11-05 2023-05-02 Veracyte, Inc. Methods for nucleic acid sequencing
US11873532B2 (en) 2017-03-09 2024-01-16 Decipher Biosciences, Inc. Subtyping prostate cancer to predict response to hormone therapy
US11976329B2 (en) 2013-03-15 2024-05-07 Veracyte, Inc. Methods and systems for detecting usual interstitial pneumonia

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0111027A1 (de) * 1982-12-13 1984-06-20 Knut Steins Verfahren zur Frühestbestimmung der Gravidität, insbesondere beim Menschen sowie zur Durchführung dieses Verfahrens besonders geeignete Testreagenz

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3059524A (en) * 1958-06-04 1962-10-23 Grassmann Wolfgang Method and apparatus for the continuous colorimetric determination of the individualcomponents of a mixture
US3235336A (en) * 1963-06-20 1966-02-15 Beckman Instruments Inc Method and apparatus for determining iodine in organic and biological materials
US3389968A (en) * 1966-07-07 1968-06-25 Huis Clinical Lab Inc Method of determining thyroxin iodine in blood serum
US3494744A (en) * 1967-10-26 1970-02-10 Bio Rad Laboratories Method for determination of proteinbound iodinated components

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3059524A (en) * 1958-06-04 1962-10-23 Grassmann Wolfgang Method and apparatus for the continuous colorimetric determination of the individualcomponents of a mixture
US3235336A (en) * 1963-06-20 1966-02-15 Beckman Instruments Inc Method and apparatus for determining iodine in organic and biological materials
US3389968A (en) * 1966-07-07 1968-06-25 Huis Clinical Lab Inc Method of determining thyroxin iodine in blood serum
US3494744A (en) * 1967-10-26 1970-02-10 Bio Rad Laboratories Method for determination of proteinbound iodinated components

Cited By (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3874794A (en) * 1972-04-21 1975-04-01 Bodenseewerk Perkin Elmer Co Method and apparatus for photometric analysis of substantially colorless components of sample
US10494677B2 (en) 2006-11-02 2019-12-03 Mayo Foundation For Medical Education And Research Predicting cancer outcome
US10865452B2 (en) 2008-05-28 2020-12-15 Decipher Biosciences, Inc. Systems and methods for expression-based discrimination of distinct clinical disease states in prostate cancer
US10407731B2 (en) 2008-05-30 2019-09-10 Mayo Foundation For Medical Education And Research Biomarker panels for predicting prostate cancer outcomes
US10114924B2 (en) 2008-11-17 2018-10-30 Veracyte, Inc. Methods for processing or analyzing sample of thyroid tissue
US10672504B2 (en) 2008-11-17 2020-06-02 Veracyte, Inc. Algorithms for disease diagnostics
EP3831954A2 (de) 2008-11-17 2021-06-09 Veracyte, Inc. Verfahren und zusammensetzungen zur molekularen profilierung für die diagnose von erkrankungen
US10236078B2 (en) 2008-11-17 2019-03-19 Veracyte, Inc. Methods for processing or analyzing a sample of thyroid tissue
EP3467123A2 (de) 2008-11-17 2019-04-10 Veracyte, Inc. Verfahren und zusammensetzungen zur molekularen profilierung für die diagnose von erkrankungen
EP3029158A1 (de) 2008-11-17 2016-06-08 Veracyte, Inc. Verfahren und zusammensetzungen zur molekularen profilerstellung für die diagnose von erkrankungen
US10422009B2 (en) 2009-03-04 2019-09-24 Genomedx Biosciences Inc. Compositions and methods for classifying thyroid nodule disease
US10934587B2 (en) 2009-05-07 2021-03-02 Veracyte, Inc. Methods and compositions for diagnosis of thyroid conditions
EP3360978A2 (de) 2009-05-07 2018-08-15 Veracyte, Inc. Verfahren zur diagnose von schilddrüsenerkrankungen
US10731223B2 (en) 2009-12-09 2020-08-04 Veracyte, Inc. Algorithms for disease diagnostics
US10446272B2 (en) 2009-12-09 2019-10-15 Veracyte, Inc. Methods and compositions for classification of samples
US9856537B2 (en) 2009-12-09 2018-01-02 Veracyte, Inc. Algorithms for disease diagnostics
WO2011143361A2 (en) 2010-05-11 2011-11-17 Veracyte, Inc. Methods and compositions for diagnosing conditions
US10513737B2 (en) 2011-12-13 2019-12-24 Decipher Biosciences, Inc. Cancer diagnostics using non-coding transcripts
US11035005B2 (en) 2012-08-16 2021-06-15 Decipher Biosciences, Inc. Cancer diagnostics using biomarkers
WO2014151764A2 (en) 2013-03-15 2014-09-25 Veracyte, Inc. Methods and compositions for classification of samples
US11976329B2 (en) 2013-03-15 2024-05-07 Veracyte, Inc. Methods and systems for detecting usual interstitial pneumonia
US11639527B2 (en) 2014-11-05 2023-05-02 Veracyte, Inc. Methods for nucleic acid sequencing
US11414708B2 (en) 2016-08-24 2022-08-16 Decipher Biosciences, Inc. Use of genomic signatures to predict responsiveness of patients with prostate cancer to post-operative radiation therapy
US11208697B2 (en) 2017-01-20 2021-12-28 Decipher Biosciences, Inc. Molecular subtyping, prognosis, and treatment of bladder cancer
US11873532B2 (en) 2017-03-09 2024-01-16 Decipher Biosciences, Inc. Subtyping prostate cancer to predict response to hormone therapy
US11078542B2 (en) 2017-05-12 2021-08-03 Decipher Biosciences, Inc. Genetic signatures to predict prostate cancer metastasis and identify tumor aggressiveness
US11217329B1 (en) 2017-06-23 2022-01-04 Veracyte, Inc. Methods and systems for determining biological sample integrity

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Publication number Publication date
AT277936B (de) 1970-01-12
DE1910056A1 (de) 1969-10-02

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