Scandinavian Journal of Clinical and Laboratory Investigation
ISSN: 0036-5513 (Print) 1502-7686 (Online) Journal homepage: http://www.tandfonline.com/loi/iclb20
Nomenclature of Reagents A. Uldall & R. Dybkær To cite this article: A. Uldall & R. Dybkær (1976) Nomenclature of Reagents, Scandinavian Journal of Clinical and Laboratory Investigation, 36:4, 305-312, DOI: 10.1080/00365517609055265 To link to this article: http://dx.doi.org/10.1080/00365517609055265
Published online: 14 Feb 2011.
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Date: 19 June 2016, At: 02:56
Scand. 1. d i n . Lab. Invest., Vol. 36, 1976.
EDITORIAL Nomenclature of Reagents Any reagent can be regarded as a system, and its use, in the simplest form, may be illustrated by the relation Original system Reagent system + Measuring system The Original system, in clinical chemistry, often is a part of a human body or its excretions, e.g. blood or urine. A more complex situation is Original system -I-Reagent system 1 + Intermediate system Intermediate system Reagent system 2 -+ Measuring system In some cases, the Original system may also be classified as a reagent, c.g. when calibration and control materials are used in place of specimen. The term ‘reagent’ comprises pure substances and mixtures, whether they be gaseous, liquid, or solid. The many reagents used today in analytical work are named and described according to various rules. The lack of uniformity and information will be found in handbooks (1, 2, 18, 22), scientific papers, and local analytical instructions, where coloquial and trivial names are common. The situation is unfortunate, since a correct and sufficiently informative reagent name is a prerequisite for relevant interchange of information about analytical methods and, thereby, for acceptable analytical work with minimal effort. If international recommendations for nomenclature of reagents used in clinical chemistry are to be made, it seems reasonable to base them on the Recommendations issued by International Union of Pure and Applied Chemistry (IUPAC), International Union of Biochemistry (IUB), International Federation of Clinical Chemistry (IFCC), International Committee of Standardization in Hematology (ICSH), World Association of Societies of Pathology (WASP), and World Health Organization (WHO). In connection with the IUPAC-IFCC Recommendation 1966 (8) some suggestions for constructing quantity names were made, and they may be applied to the present problem. These suggestions were recently stated as a Recommendation (17).
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PROBLEMS OF PRESENT USAGE The usual reagent description is ambiguous and deficient both as regards names, numerical values, and units. Jargon names for reagents and their components are often confusing and convey insufficient chemical information as evidenced by the following examples: ‘Drabkin’s solution’ (4, 7, 21, 23, 25); ‘saline’ or even ‘physiological saline’, which may have different concentrations of sodium chloride; ‘citrate 3.80/,* made from different chemicals; DMSO; 5HT; LDH; BSP; EDTA 1 - Scand. J. clin. Lab. Invest
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with unspecified cation; exclusive use of proprieiary names. Even when a reagent is described in more detail the present tendency is to give production data instead of what is of real interest: the properties of the reagent for use. It is seldom realized that a single numerical value is insufficient to indicate both the magnitude and variation of a quantity because different technologies have different and varying, often unspecified, conventions. This is especially unfortunate in reagent designations for labels where the pharmacist, chemist, and physicist handle the same bottle. WHO (27) stipulates that for control results of pharmaceutical preparations, the figure 100, e.g., means >99.5 to 5100.5. The interval is not regarded as a tolerance interval, i.e. no result is allowed outside. This rigid convention may have some merit to a pharmacist, also as an instruction for preparation. However, it is difficult to follow when conversions to other kinds of quantities and units yield ‘broken’ figures. Moreover, the rule becomes impractical for results that have been determined with a rather large coefficient of variation. For example, if the confidence interval of the result 100 is 1.2-i.e. the ‘true value’ lies in the interval 299.4 to 5 100.6 (with a certain probability). However, the WHO convention forces us to write 10 x lo‘, corresponding to the unnecessarily wide interval of >95 to 5 105. Whichever convention one adopts for implied interval about the last digit(s), the decimal system precludes a smooth relationship with the actual analytical confidence interval. This is true both for some chemists’ convention of a variation of f 1 about the last digit and the physicists’ analogous rules of * 5 o r * 10. In this connection it should be mentioned that the meaning of the two for ‘approximately equal to’ and for ‘equal to’ has not been signs : defined statistically. The problems of units are several. 1. Outdated units and symbols, e.g. mp -+ nm; gms. g; M moI/I (19, 20). 2. The kinds of quantities are omitted and implied by the unit, e.g. mollkg is taken to mean ‘molality’ but would apply equally to ‘amount of substance of component per mass of mixture’ and to ‘ionic strength’. 3. Different conventions of such implications are often followed, e.g. ‘per cent’ according to International Pharmacopoeia ~(27)means mass per volume of water, whereas Pharmacopoea Nordica (5,6) generally implies mass in mass. -+
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PROPOSED STRUCTURE OF REAGENT DESIGNATIONS AND NAMES The reagent monograph is the most comprehensive information available about a reagent. In a scientific paper it is given under Materials. It tells about production and all relevant properties of the finished product. The generic monograph is the presentation of the properties that production should aim at, with numerical data, preferably in a statistical presentation, and control
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procedures. The individual monograph is specific for a certain batch or portion of a produced reagent and includes statistical results of control measures. In most situations the entire monograph is cumbersome and unnecessary; a shorter reagent designation is chosen. This comprises the reagent reference and salient properties of the reagent in the generic or individual form; it is often used for the more elaborate label of the reagent container. It should be noted that the reagent designation is not necessarily suitable as a recipe for production. The reagent ncrme, generic or individual, may be even shorter, stating the reagent reference and a characteristic, suitable for quick identification. This name is often used in the running text of publications. The shortest possible name is a reagent reference or system identification, generic or individual, indicating where infopmation can be found about production and properties. The reagent reference is always a part of the reagent name and is also included in the reagent designation and monograph. The following format of reagent reference, name, and designation is based on Recommendations from IUPAC-IFCC (16, 17), where any quantity is given according to the scheme System-Component, kind of quantity = numerical value . unit Each of the three parts of the name may have specifications in parentheses. Any reagent is treated as a system, containing components and having properties, defined through kinds of quantities, for which values can be given. System
The system, in the present context, is the reagent. The generic reagent reference refers to a published or local monograph. Thus, Reagent(Pharmacopoeia Internationalis 1967, 2. ed., p. 665, 1. 8)is an adequate generic reagent reference. It does not, of course, explicitly indicate a system of an ‘ethanolic sodium hydroxide’. Locally this reagent could have a shorter reference leading to the laboratory manual of, e.g., United States’ National Bureau of Standards: R(N BS- 10375)The individual reagent reference should contain batch number or date referring to a production record with details. Component
A component is a definable part of a system and may be physical (Erythrocyte), chemical (Hemoglobin(Fe)), or functional (Lactate dehydrogenase(EC 1.1.1.27)). Its name should be reasonably systematic according to international recommendations, mainly from IUPAC-IFCC (17), IUB (3, lo), IUPAC (11-19, as well as WHO (26). One, a few, or all of the components in the system are presented in the designation or name, according to which information is deemed essential.
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Kind of quantity
A kind of quantity defines how system and component should be regarded in order to obtain a value. Thus ‘substanceconcentration’tells that the amount of substance (in moles) of the component should be divided by the system volume (in litres). The inclusion of the kind of quantity in the quantity name is mandatory the unit cannot substitute or explain the kind of quantity, since several kinds of quantities may use the same unit. (For example, the unit mol/kg is used for substance content, ionic strength, and molality.) In accordance with chemical and biochemical practice and the recent joint Recommendation from ICSH, IFCC, and WAPS (9), it 3s recommended that ‘molecular’ kind3 of quantities, i.e. those based on ‘amount of substance’ (unit ‘mole’), should be preferred to Ikinds of quantities based on ‘mass’ (unit ‘kilogram’).Considerable extra chemical information is obtained in this way. It should be mentioned that the ambiguous concept ‘equivalent’ and the related ‘normality’ (symbolized N) are being discouraged (8, 16). But it is often necessary to state the relevant elementary entity of the component: Hemoglobin(l6 115), Calcium(I1) (Ca0J.
Numerical value
Obvbusly, the several already described conventions d implied fixed (confidence?) intervals about one numerical vdue are insufficient and ambiguous. The number of digits may vary with what the figure is used for: rough estimate or further statistical calculations. However, the digits of the primary data should not be augmented by ‘empty’ digits, and the number of digits in the final result should be restricted by common sense. In generic names, designations, and monographs each representative numerical value should be accompanied by a confidence interval with stated probability based on the prescribed procedure for production. In individual names, designations, and monographs each representative numerical value should be accompanied by suitable classical or ‘distributionfree’ statistics obtained from actual cproduction control measurements of the reagent properties. If a Gaussian distribution of control data may be assumed, it is sufficiently descriptive to state the observed arithmetic mean (x) and, in parentheses, the number of actual estimations (n), the best estimate of the usual standard deviation of control measurement usual)), and the actual standard deviation @(actual)) if the size of n makes it relevant. When a distribution-free presentation is chosen, the median (or 0.5 fractile) may be preferred to the arithmetic mean: Xl(P=O.S), where XI stands for the value registered at the comubtive number fraction P=0.5; i.e. half of the values are equal to or less than the value XI. The usual and actual dispersions are given in parentheses as interfractile intervals together with the number of observations, e.g., for the actual dispersion (n= 10; x ~ ( P = 0 . 2 ) ,x3(P=0.8)). When control measurements are lacking, the confidence intervals from the generic presentation are used.
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Unit In general, the seven base and many coherent units of the Intertzational System of Units (SI units) (20) should be used (9). The SI base units comprise metre (rn), kilogram (kg), second (s), ampere (A), kelvin (K), candela (cd), and mole (mol). In addition, IUPAC recommends katal (kat), functioning as a base unit for catalytic amount (16). (The kind of quantity name ‘catalytic amount’ may be changed t o ‘catalytic ability’ by IFCC-IUPAC.) The coherent units are constructed by multiplication and division of base units. Practical sizes are obtained by S I prefixes that are powers of ten; Ion, where n is a n integer. The list stretches from exa (E = lola) to atto (a = 10-lx), and those factors that arc lWn are especially preferred since they facilitate conversions; i.e. the SI prefixes hecto, deca, deci, and centi are not reommended. In derived units all powers of ten should be collected in one factor (often symbolized), placed at the beginning of a product or in the numerator of a fraction; an exception is made for the base unit kilogram. In clinical chemistry, one officially permitted exception (9, 16) to the SI is made by preferring litre (=lo-3 m3 exactly) to m3 or dms. Thus, a series of subunits with steps of lo3 is obtained using the Sl prefixes 103” on the litre. With kinds of quantities having the dimension one, the coherent unit is ‘unity’ (= 1). For example, relative density and volume fraction both use the unit ‘1’. and not ‘(kg/l)/ (kgll)’ and ’l/l’ respectively. Here, SI factor names and symbols cannot be employed since the unit ‘unity’ does not, yet, have an internationally approved name; (lo::{ x 1, not 1 milli = 1 rn, which would be confused with one metre),
Formiit
In the designation of a reagent, the system, indicated by the reference, and each of the sets stating component, kind of quantity, and value are often given in separate lines: R(reference)Component 1, kind of quantity = a X unit (statistics); Component 2, kind of quantity = b X unit (statistics); etc. The selection among the innumerable quantities which describe a reagent is arbitrary and varies with the knowledge of the system and the purpose of the text, but known components (apart from impurities presumed to be unimportant) usually appear as part of the quantity names constituting the designation. The sequence of properties is also arbitrary, but the most significant are given first. In order to save space, the designation may be given in continuous text with semicolons between quantities. Where doubt may arise about the beginning and end of a given designation, this can be bracketed: [R(reference)Component 1, kind of quantity = a X unit (statistics); Component 2; etc.], where ‘etc.’ may be used to indicate that other known components are not mentioned. A name, usually, is a more or less truncated part of the designation. Thus the name could indicate a single, fully specified property: R(reference&Componertt 1, kind of quantity = a x unit (statistics) or might be cut down to the name R(reference)-Component 1 or even R4omponent 1
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where the shortest name is intended for repeated use in a text when the entire monograph (or designation) is given under Materials. EXAMPLE The set of recommendations given above may be illustrated by a well-known reagent used for the determination of hemoglobin concentration in blood according to van Kampen & Zijlstra (24). According to the classical way of giving data derived rather directly from the instruction for production, this reagent could bear the following ‘designation’ on the label:
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Potassium cyanide Potassium ferricyanide Potassium biphosphate Sterox SE8 pH 7.2
0.77 mrnol/l 0.61 mmol/l 1.03 mmol/l
0.5
rnVI
The present proposal, stressing the properties of the finished product and the use of rules for naming quantities, would lead to the following generic reagent designation (using the abbreviations: substc. for substance concentration and volfr. for volume fraction). R(van Kampen, G. J. & Zijktra, W. G., Clin. chm. Acta 6,1961, 538-544)Cyanide, substc. = 0.77 mmol/l (S = 0.006 mmol,/l); Hexacyanoferrate(III),substc. = 0.61 mmol/l (s = 0.005 mmol/l); PhOSpbate, ~ubsk.= 1.03 LIIUIOI/I (S = 0.009 mm0V1); Sterox SE8, volfr. = 0.5 X 10-3 (s = 0.05 X 10-3); Potassium ion, substc. = 3.63 mmol/l (s = 0.014 mmol/l); Water, substc. = 55 mol/l; pH(T = 293 K) = 7.2 (S = 0.05)
The source of phosphate may be potassium dihydrogenphosphate or orthophosphoric acid. The final Concentration of potassium ion is obtained from three salts or from two salts and potassium hydroxide. (In the monograph the properties of all chemicals should be stated; e.g. for water, ‘de-ionized’ with stated conductance.) The standard deviations (s} would be obtained (according to previous experience) if repeated productions of the reagent were made (and controlled) according to the monograph. In the text of a scientific paper comparing different cyanidecontaining reagents, this long designation might be cut down to 0.77 mmol/l; etc.] IR(ref. 7tcyaoide, sub&. and the reader interested in further details of the system ‘R(ref. 7)’ would have to look it up in Reference 7. The same reagent routinely used in, e.g., United States’ Center for Disease Control could be named R(CDC 10473; batch no. 51)-Cyanide if the concentration was not so important because there was no other cyanide solution available.
CONCLUSION The many reagents (pure substances or mixtures) used today in analytical work are named according to various rules, and the nomenclature is often insufficient and ambiguous. A reagent is a system containing components and having properties - defined through kinds of quantities - for which values can be given. The Recommendations from IUPAC-IFCC are suitable for creating a framework for a systematic reagent nomenclature.
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The recommended format: System-Component, kind of quantity = numerical value . unit (statistics) is applied to the present problem. The reagent is the system which always has specifications in the form of a reagent reference to a detailed monograph and it may include a batch number. The reagent designation consists of all known relevant properties given according to the above format. The reagent name is one or a few essential properties described likewise, but with the length truncated according to needs. The flexibility and information content is exemplified. A. Uldall & R. Dybker Department of Clinical Chemistry Geriatric Unit, De Gamles By DK-2200 Copenhagen N, Denmark
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ACKNOWLEDGEMENT The authors wish to thank helpful colleagues, and especially Dr. Kjeld Jorgensen, for stimulating discussions. Note. The IS0 and IUPAC-IFCC recommended use of a comma as decimal sign has not been employed in this paper due to Editorial policy. REFERENCES
I . Bollinger, H. R., Brenner. M., Ganshirt, H., Mangold, H. K., Seiler, H., Stahl, E. (ed.) & Waldi, D. Thin-Layer Chromatography. Springer Verlag, Berlin, Heidelberg, New York; Academic Press Inc., Publishers, New York, London, 1%5. 2. Boutwell, J. H., Jr. Clinical Chemistry, Laboratory Manual and Methods. Lea & Febiger, Philadelphia. 1961. 3. Commision on Biochemical Nomenclature (CBN). Enzyme Nomenclature, Recommendations (1972) of International Union of Pure and Applied Chemistry and Znternarional Union of Biochemistry. Elsevier Scientific Publishing Co., Amsterdam, 1973. 4. Crosby. W. H., Munn, J . I. & Furth, F. W. Standardizing a method for clinical hemoglobinometry. U . S . Armed Forces med. J . 5 , 693, 1954. 5. Dzn Danske Farmakopekommission. p. 67 in Pharmacopoea Nordica, ZW3. Editio Danica, Vol. I . Nyt Nordisk Forlag Arnold Busck, Copenhagen, 1953. 6 . Den Danske Farmakopkkommission. p. 109 in Pharmacopoea Nordica, 1963, Editio Danica, Vol. 111. Nyt Nordisk Forlag Arnold Busck, Copenhagen, 1963. 7. Drabkin, D. L. & Austin, J. H. Spectrophotornetric studies. 11. Preparations from washed blood cells: nitric oxide hemoglobin and sulfhemoglobin. 1. biol. Chem. 112, 51, 1935. 8. Dybkser, R . & Jorgensen. K. Quantities and Units in Clinical Chemistry. Including Recommendation 1966 of the Commission on Clinical Chemistry of the International Union of Pure and Applied Chemistry and of the International Federation f o r Clinical Chemistry. Munksgaard, Copenhagen, 1%7. 9. International Committee for Standardization in Hematology (ICSH), International Federation of Clinical Chemistry (IFCC) & World Association of (Anatomic and Clinical) Pathology Societies (WAPS). Recommendation for use of SI in clinical laboratory measurements. Z. klin. Chem. 11, 93, 1973. 10. International Union of Pure and Applied Chemistry & International Union of Biochemistry. Collected Tentatii,e Rules & Recommendations of the Commission on Biochemical Nomenclature. Reprint by American Society of Biological Chemists, Inc., Bethesda, Maryland, 1973. 1 1 . International Union of Pure and Applied Chemistry, Commission on the Nomenclature o f Inorganic Chemistry. Nomenclature o f Inorganic Chemistry, Definitive Rules 1970, 2nd ed. Butterworths, London, 1971.
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12. International Union of Pure and Applied Chemistry, Commission on the Nomenclature of Organic Chemistry. Nomenclature of Organic Chemistry, Definitive Rules for Section A. Hydrocarbons; Section B. Fundamental Heterocyclic Systems; Section C. Characteristic Groups Containing Carbon, Hydrogen, Oxygen, Nitrogen, Halogen, Sulfur, Selenium, andf or Tellurium. Buttenvorths, London, 197 1. 13. International Union of Pure and Applied Chemistry, Commission on the Nomenclature of Organic Chemistry. Tentative Rules for the Nomenclature of Organic Chemistry for Section E, Fundamental Stereochemistry. IUPAC Information Bulletin, No. 35, 36, 1969. 14. International Union of Pure and Applied Chemistry, Cornmission on Nomenclature of Inorganic Chemistry & Commission on Nomenclature of Organic Chemistry. (Tentative rules of) Nomenclature of Organic Chemistry for Section D. Organic element compounds. IUPAC Information Bulletin, Appendices on Tentative Nomenclature, Symbols, Units, and Standards, No. 31, 1973. 15. International Union of Pure and Applied Chemistry, Commission o n the Nomenclature of Organic Chemistry. Tentative RuIes for Section X. Natural Products and Related Compounds. In preparation. 16. International Union of Pure and Applied Chemistry, Section on Clinical Chemistry, Commission on Quantities and Units & International Federation for Clinical Chemistry, Committee on Standards, Expert Panel o n Quantities and Units. Quantities and units in clinical chemistry. Recommendation 1973. Pure appl. Chem. 37, 517, 1974. 17. International Union of Pure and Applied Chemistry, Section on Clinical Chemistry, Commission on Quantities and Units & International Federation for Clinical Chemistry, Committee on Standards, Expert Panel on Quantities and Units. List of quantities in clinical chemistry. Recommendation 1973. Pure appl. Chem. 37, 547, 1974. 18. Krupp, M. A., Sweet, N. J., Jawetz, E. & Biglien, E. G. Physician’s Handbook, 15th ed. Blackwell Scientific Pulblications, Oxford and Edinburgh, 1968. 19. McGlashan, M. L. Physicochemical Quantities and Units, 2nd ed. The Royal Institute of Chemistry, London, 197 1. 20. National Physical Laboratory. SI, The International System of Units. Her Majesty’s Stationery Office, London, 1970. 21. Richterich, R. Ktinische Chemie, Theorie und Praxis, 2nd ed. Akademische Verlagsgesellschaft, Frankfurt a.M., 1968. 22. Sjoblom, C. G. & Sundberg, B. Reagensboken, Beredning av Reagens pd Apotek. Svenska Bokforlaget, 1969. 23. Stadie, W. C. A method for the determination of methemoglobin in blood. J. biol. Chem. 41, 237, 1920. 24. van Kampen, E. J. & Zijlstra, W. G. Standardization of hemoglobinometry. 11. The hemiglobincyanide method. Clin. chim. Acta 6, 538, 1961. 25. v. Klein-Wisenberg, A. in de Boroviczhy, C. G. (ed.)Standardization in Haematology 111. S. Karger, Basel, New York, 1966; also in Bibl. haemat. (Basel) 24, 150, 1966.
26. World Health Organization. Cumulative List No. 3 of Proposed International Nonproprietary Names f o r Pharmaceutical Substances. Lists 1-25 published in World Health Organization Chronicle, nos. 7-25 (1 953-1 9 1 ) , World Health Organization, Geneva, 197 1. 27. World Health Organization, Expert Committee o n Specifications for Pharmaceutical Preparations. pp. XXXTI, XXXIV in Specifications f o r the Quality Control o f Pharmaceutical Preparations. International Pharmacopoeia, 2nd ed. World Health Organization, Geneva, 1967.
ISSN: 0036-5513 (Print) 1502-7686 (Online) Journal homepage: http://www.tandfonline.com/loi/iclb20
Nomenclature of Reagents A. Uldall & R. Dybkær To cite this article: A. Uldall & R. Dybkær (1976) Nomenclature of Reagents, Scandinavian Journal of Clinical and Laboratory Investigation, 36:4, 305-312, DOI: 10.1080/00365517609055265 To link to this article: http://dx.doi.org/10.1080/00365517609055265
Published online: 14 Feb 2011.
Submit your article to this journal
Article views: 1
View related articles
Citing articles: 2 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=iclb20 Download by: [La Trobe University]
Date: 19 June 2016, At: 02:56
Scand. 1. d i n . Lab. Invest., Vol. 36, 1976.
EDITORIAL Nomenclature of Reagents Any reagent can be regarded as a system, and its use, in the simplest form, may be illustrated by the relation Original system Reagent system + Measuring system The Original system, in clinical chemistry, often is a part of a human body or its excretions, e.g. blood or urine. A more complex situation is Original system -I-Reagent system 1 + Intermediate system Intermediate system Reagent system 2 -+ Measuring system In some cases, the Original system may also be classified as a reagent, c.g. when calibration and control materials are used in place of specimen. The term ‘reagent’ comprises pure substances and mixtures, whether they be gaseous, liquid, or solid. The many reagents used today in analytical work are named and described according to various rules. The lack of uniformity and information will be found in handbooks (1, 2, 18, 22), scientific papers, and local analytical instructions, where coloquial and trivial names are common. The situation is unfortunate, since a correct and sufficiently informative reagent name is a prerequisite for relevant interchange of information about analytical methods and, thereby, for acceptable analytical work with minimal effort. If international recommendations for nomenclature of reagents used in clinical chemistry are to be made, it seems reasonable to base them on the Recommendations issued by International Union of Pure and Applied Chemistry (IUPAC), International Union of Biochemistry (IUB), International Federation of Clinical Chemistry (IFCC), International Committee of Standardization in Hematology (ICSH), World Association of Societies of Pathology (WASP), and World Health Organization (WHO). In connection with the IUPAC-IFCC Recommendation 1966 (8) some suggestions for constructing quantity names were made, and they may be applied to the present problem. These suggestions were recently stated as a Recommendation (17).
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PROBLEMS OF PRESENT USAGE The usual reagent description is ambiguous and deficient both as regards names, numerical values, and units. Jargon names for reagents and their components are often confusing and convey insufficient chemical information as evidenced by the following examples: ‘Drabkin’s solution’ (4, 7, 21, 23, 25); ‘saline’ or even ‘physiological saline’, which may have different concentrations of sodium chloride; ‘citrate 3.80/,* made from different chemicals; DMSO; 5HT; LDH; BSP; EDTA 1 - Scand. J. clin. Lab. Invest
Downloaded by [La Trobe University] at 02:56 19 June 2016
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with unspecified cation; exclusive use of proprieiary names. Even when a reagent is described in more detail the present tendency is to give production data instead of what is of real interest: the properties of the reagent for use. It is seldom realized that a single numerical value is insufficient to indicate both the magnitude and variation of a quantity because different technologies have different and varying, often unspecified, conventions. This is especially unfortunate in reagent designations for labels where the pharmacist, chemist, and physicist handle the same bottle. WHO (27) stipulates that for control results of pharmaceutical preparations, the figure 100, e.g., means >99.5 to 5100.5. The interval is not regarded as a tolerance interval, i.e. no result is allowed outside. This rigid convention may have some merit to a pharmacist, also as an instruction for preparation. However, it is difficult to follow when conversions to other kinds of quantities and units yield ‘broken’ figures. Moreover, the rule becomes impractical for results that have been determined with a rather large coefficient of variation. For example, if the confidence interval of the result 100 is 1.2-i.e. the ‘true value’ lies in the interval 299.4 to 5 100.6 (with a certain probability). However, the WHO convention forces us to write 10 x lo‘, corresponding to the unnecessarily wide interval of >95 to 5 105. Whichever convention one adopts for implied interval about the last digit(s), the decimal system precludes a smooth relationship with the actual analytical confidence interval. This is true both for some chemists’ convention of a variation of f 1 about the last digit and the physicists’ analogous rules of * 5 o r * 10. In this connection it should be mentioned that the meaning of the two for ‘approximately equal to’ and for ‘equal to’ has not been signs : defined statistically. The problems of units are several. 1. Outdated units and symbols, e.g. mp -+ nm; gms. g; M moI/I (19, 20). 2. The kinds of quantities are omitted and implied by the unit, e.g. mollkg is taken to mean ‘molality’ but would apply equally to ‘amount of substance of component per mass of mixture’ and to ‘ionic strength’. 3. Different conventions of such implications are often followed, e.g. ‘per cent’ according to International Pharmacopoeia ~(27)means mass per volume of water, whereas Pharmacopoea Nordica (5,6) generally implies mass in mass. -+
-+
PROPOSED STRUCTURE OF REAGENT DESIGNATIONS AND NAMES The reagent monograph is the most comprehensive information available about a reagent. In a scientific paper it is given under Materials. It tells about production and all relevant properties of the finished product. The generic monograph is the presentation of the properties that production should aim at, with numerical data, preferably in a statistical presentation, and control
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procedures. The individual monograph is specific for a certain batch or portion of a produced reagent and includes statistical results of control measures. In most situations the entire monograph is cumbersome and unnecessary; a shorter reagent designation is chosen. This comprises the reagent reference and salient properties of the reagent in the generic or individual form; it is often used for the more elaborate label of the reagent container. It should be noted that the reagent designation is not necessarily suitable as a recipe for production. The reagent ncrme, generic or individual, may be even shorter, stating the reagent reference and a characteristic, suitable for quick identification. This name is often used in the running text of publications. The shortest possible name is a reagent reference or system identification, generic or individual, indicating where infopmation can be found about production and properties. The reagent reference is always a part of the reagent name and is also included in the reagent designation and monograph. The following format of reagent reference, name, and designation is based on Recommendations from IUPAC-IFCC (16, 17), where any quantity is given according to the scheme System-Component, kind of quantity = numerical value . unit Each of the three parts of the name may have specifications in parentheses. Any reagent is treated as a system, containing components and having properties, defined through kinds of quantities, for which values can be given. System
The system, in the present context, is the reagent. The generic reagent reference refers to a published or local monograph. Thus, Reagent(Pharmacopoeia Internationalis 1967, 2. ed., p. 665, 1. 8)is an adequate generic reagent reference. It does not, of course, explicitly indicate a system of an ‘ethanolic sodium hydroxide’. Locally this reagent could have a shorter reference leading to the laboratory manual of, e.g., United States’ National Bureau of Standards: R(N BS- 10375)The individual reagent reference should contain batch number or date referring to a production record with details. Component
A component is a definable part of a system and may be physical (Erythrocyte), chemical (Hemoglobin(Fe)), or functional (Lactate dehydrogenase(EC 1.1.1.27)). Its name should be reasonably systematic according to international recommendations, mainly from IUPAC-IFCC (17), IUB (3, lo), IUPAC (11-19, as well as WHO (26). One, a few, or all of the components in the system are presented in the designation or name, according to which information is deemed essential.
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Kind of quantity
A kind of quantity defines how system and component should be regarded in order to obtain a value. Thus ‘substanceconcentration’tells that the amount of substance (in moles) of the component should be divided by the system volume (in litres). The inclusion of the kind of quantity in the quantity name is mandatory the unit cannot substitute or explain the kind of quantity, since several kinds of quantities may use the same unit. (For example, the unit mol/kg is used for substance content, ionic strength, and molality.) In accordance with chemical and biochemical practice and the recent joint Recommendation from ICSH, IFCC, and WAPS (9), it 3s recommended that ‘molecular’ kind3 of quantities, i.e. those based on ‘amount of substance’ (unit ‘mole’), should be preferred to Ikinds of quantities based on ‘mass’ (unit ‘kilogram’).Considerable extra chemical information is obtained in this way. It should be mentioned that the ambiguous concept ‘equivalent’ and the related ‘normality’ (symbolized N) are being discouraged (8, 16). But it is often necessary to state the relevant elementary entity of the component: Hemoglobin(l6 115), Calcium(I1) (Ca0J.
Numerical value
Obvbusly, the several already described conventions d implied fixed (confidence?) intervals about one numerical vdue are insufficient and ambiguous. The number of digits may vary with what the figure is used for: rough estimate or further statistical calculations. However, the digits of the primary data should not be augmented by ‘empty’ digits, and the number of digits in the final result should be restricted by common sense. In generic names, designations, and monographs each representative numerical value should be accompanied by a confidence interval with stated probability based on the prescribed procedure for production. In individual names, designations, and monographs each representative numerical value should be accompanied by suitable classical or ‘distributionfree’ statistics obtained from actual cproduction control measurements of the reagent properties. If a Gaussian distribution of control data may be assumed, it is sufficiently descriptive to state the observed arithmetic mean (x) and, in parentheses, the number of actual estimations (n), the best estimate of the usual standard deviation of control measurement usual)), and the actual standard deviation @(actual)) if the size of n makes it relevant. When a distribution-free presentation is chosen, the median (or 0.5 fractile) may be preferred to the arithmetic mean: Xl(P=O.S), where XI stands for the value registered at the comubtive number fraction P=0.5; i.e. half of the values are equal to or less than the value XI. The usual and actual dispersions are given in parentheses as interfractile intervals together with the number of observations, e.g., for the actual dispersion (n= 10; x ~ ( P = 0 . 2 ) ,x3(P=0.8)). When control measurements are lacking, the confidence intervals from the generic presentation are used.
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Unit In general, the seven base and many coherent units of the Intertzational System of Units (SI units) (20) should be used (9). The SI base units comprise metre (rn), kilogram (kg), second (s), ampere (A), kelvin (K), candela (cd), and mole (mol). In addition, IUPAC recommends katal (kat), functioning as a base unit for catalytic amount (16). (The kind of quantity name ‘catalytic amount’ may be changed t o ‘catalytic ability’ by IFCC-IUPAC.) The coherent units are constructed by multiplication and division of base units. Practical sizes are obtained by S I prefixes that are powers of ten; Ion, where n is a n integer. The list stretches from exa (E = lola) to atto (a = 10-lx), and those factors that arc lWn are especially preferred since they facilitate conversions; i.e. the SI prefixes hecto, deca, deci, and centi are not reommended. In derived units all powers of ten should be collected in one factor (often symbolized), placed at the beginning of a product or in the numerator of a fraction; an exception is made for the base unit kilogram. In clinical chemistry, one officially permitted exception (9, 16) to the SI is made by preferring litre (=lo-3 m3 exactly) to m3 or dms. Thus, a series of subunits with steps of lo3 is obtained using the Sl prefixes 103” on the litre. With kinds of quantities having the dimension one, the coherent unit is ‘unity’ (= 1). For example, relative density and volume fraction both use the unit ‘1’. and not ‘(kg/l)/ (kgll)’ and ’l/l’ respectively. Here, SI factor names and symbols cannot be employed since the unit ‘unity’ does not, yet, have an internationally approved name; (lo::{ x 1, not 1 milli = 1 rn, which would be confused with one metre),
Formiit
In the designation of a reagent, the system, indicated by the reference, and each of the sets stating component, kind of quantity, and value are often given in separate lines: R(reference)Component 1, kind of quantity = a X unit (statistics); Component 2, kind of quantity = b X unit (statistics); etc. The selection among the innumerable quantities which describe a reagent is arbitrary and varies with the knowledge of the system and the purpose of the text, but known components (apart from impurities presumed to be unimportant) usually appear as part of the quantity names constituting the designation. The sequence of properties is also arbitrary, but the most significant are given first. In order to save space, the designation may be given in continuous text with semicolons between quantities. Where doubt may arise about the beginning and end of a given designation, this can be bracketed: [R(reference)Component 1, kind of quantity = a X unit (statistics); Component 2; etc.], where ‘etc.’ may be used to indicate that other known components are not mentioned. A name, usually, is a more or less truncated part of the designation. Thus the name could indicate a single, fully specified property: R(reference&Componertt 1, kind of quantity = a x unit (statistics) or might be cut down to the name R(reference)-Component 1 or even R4omponent 1
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where the shortest name is intended for repeated use in a text when the entire monograph (or designation) is given under Materials. EXAMPLE The set of recommendations given above may be illustrated by a well-known reagent used for the determination of hemoglobin concentration in blood according to van Kampen & Zijlstra (24). According to the classical way of giving data derived rather directly from the instruction for production, this reagent could bear the following ‘designation’ on the label:
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Potassium cyanide Potassium ferricyanide Potassium biphosphate Sterox SE8 pH 7.2
0.77 mrnol/l 0.61 mmol/l 1.03 mmol/l
0.5
rnVI
The present proposal, stressing the properties of the finished product and the use of rules for naming quantities, would lead to the following generic reagent designation (using the abbreviations: substc. for substance concentration and volfr. for volume fraction). R(van Kampen, G. J. & Zijktra, W. G., Clin. chm. Acta 6,1961, 538-544)Cyanide, substc. = 0.77 mmol/l (S = 0.006 mmol,/l); Hexacyanoferrate(III),substc. = 0.61 mmol/l (s = 0.005 mmol/l); PhOSpbate, ~ubsk.= 1.03 LIIUIOI/I (S = 0.009 mm0V1); Sterox SE8, volfr. = 0.5 X 10-3 (s = 0.05 X 10-3); Potassium ion, substc. = 3.63 mmol/l (s = 0.014 mmol/l); Water, substc. = 55 mol/l; pH(T = 293 K) = 7.2 (S = 0.05)
The source of phosphate may be potassium dihydrogenphosphate or orthophosphoric acid. The final Concentration of potassium ion is obtained from three salts or from two salts and potassium hydroxide. (In the monograph the properties of all chemicals should be stated; e.g. for water, ‘de-ionized’ with stated conductance.) The standard deviations (s} would be obtained (according to previous experience) if repeated productions of the reagent were made (and controlled) according to the monograph. In the text of a scientific paper comparing different cyanidecontaining reagents, this long designation might be cut down to 0.77 mmol/l; etc.] IR(ref. 7tcyaoide, sub&. and the reader interested in further details of the system ‘R(ref. 7)’ would have to look it up in Reference 7. The same reagent routinely used in, e.g., United States’ Center for Disease Control could be named R(CDC 10473; batch no. 51)-Cyanide if the concentration was not so important because there was no other cyanide solution available.
CONCLUSION The many reagents (pure substances or mixtures) used today in analytical work are named according to various rules, and the nomenclature is often insufficient and ambiguous. A reagent is a system containing components and having properties - defined through kinds of quantities - for which values can be given. The Recommendations from IUPAC-IFCC are suitable for creating a framework for a systematic reagent nomenclature.
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The recommended format: System-Component, kind of quantity = numerical value . unit (statistics) is applied to the present problem. The reagent is the system which always has specifications in the form of a reagent reference to a detailed monograph and it may include a batch number. The reagent designation consists of all known relevant properties given according to the above format. The reagent name is one or a few essential properties described likewise, but with the length truncated according to needs. The flexibility and information content is exemplified. A. Uldall & R. Dybker Department of Clinical Chemistry Geriatric Unit, De Gamles By DK-2200 Copenhagen N, Denmark
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ACKNOWLEDGEMENT The authors wish to thank helpful colleagues, and especially Dr. Kjeld Jorgensen, for stimulating discussions. Note. The IS0 and IUPAC-IFCC recommended use of a comma as decimal sign has not been employed in this paper due to Editorial policy. REFERENCES
I . Bollinger, H. R., Brenner. M., Ganshirt, H., Mangold, H. K., Seiler, H., Stahl, E. (ed.) & Waldi, D. Thin-Layer Chromatography. Springer Verlag, Berlin, Heidelberg, New York; Academic Press Inc., Publishers, New York, London, 1%5. 2. Boutwell, J. H., Jr. Clinical Chemistry, Laboratory Manual and Methods. Lea & Febiger, Philadelphia. 1961. 3. Commision on Biochemical Nomenclature (CBN). Enzyme Nomenclature, Recommendations (1972) of International Union of Pure and Applied Chemistry and Znternarional Union of Biochemistry. Elsevier Scientific Publishing Co., Amsterdam, 1973. 4. Crosby. W. H., Munn, J . I. & Furth, F. W. Standardizing a method for clinical hemoglobinometry. U . S . Armed Forces med. J . 5 , 693, 1954. 5. Dzn Danske Farmakopekommission. p. 67 in Pharmacopoea Nordica, ZW3. Editio Danica, Vol. I . Nyt Nordisk Forlag Arnold Busck, Copenhagen, 1953. 6 . Den Danske Farmakopkkommission. p. 109 in Pharmacopoea Nordica, 1963, Editio Danica, Vol. 111. Nyt Nordisk Forlag Arnold Busck, Copenhagen, 1963. 7. Drabkin, D. L. & Austin, J. H. Spectrophotornetric studies. 11. Preparations from washed blood cells: nitric oxide hemoglobin and sulfhemoglobin. 1. biol. Chem. 112, 51, 1935. 8. Dybkser, R . & Jorgensen. K. Quantities and Units in Clinical Chemistry. Including Recommendation 1966 of the Commission on Clinical Chemistry of the International Union of Pure and Applied Chemistry and of the International Federation f o r Clinical Chemistry. Munksgaard, Copenhagen, 1%7. 9. International Committee for Standardization in Hematology (ICSH), International Federation of Clinical Chemistry (IFCC) & World Association of (Anatomic and Clinical) Pathology Societies (WAPS). Recommendation for use of SI in clinical laboratory measurements. Z. klin. Chem. 11, 93, 1973. 10. International Union of Pure and Applied Chemistry & International Union of Biochemistry. Collected Tentatii,e Rules & Recommendations of the Commission on Biochemical Nomenclature. Reprint by American Society of Biological Chemists, Inc., Bethesda, Maryland, 1973. 1 1 . International Union of Pure and Applied Chemistry, Commission on the Nomenclature o f Inorganic Chemistry. Nomenclature o f Inorganic Chemistry, Definitive Rules 1970, 2nd ed. Butterworths, London, 1971.
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12. International Union of Pure and Applied Chemistry, Commission on the Nomenclature of Organic Chemistry. Nomenclature of Organic Chemistry, Definitive Rules for Section A. Hydrocarbons; Section B. Fundamental Heterocyclic Systems; Section C. Characteristic Groups Containing Carbon, Hydrogen, Oxygen, Nitrogen, Halogen, Sulfur, Selenium, andf or Tellurium. Buttenvorths, London, 197 1. 13. International Union of Pure and Applied Chemistry, Commission on the Nomenclature of Organic Chemistry. Tentative Rules for the Nomenclature of Organic Chemistry for Section E, Fundamental Stereochemistry. IUPAC Information Bulletin, No. 35, 36, 1969. 14. International Union of Pure and Applied Chemistry, Cornmission on Nomenclature of Inorganic Chemistry & Commission on Nomenclature of Organic Chemistry. (Tentative rules of) Nomenclature of Organic Chemistry for Section D. Organic element compounds. IUPAC Information Bulletin, Appendices on Tentative Nomenclature, Symbols, Units, and Standards, No. 31, 1973. 15. International Union of Pure and Applied Chemistry, Commission o n the Nomenclature of Organic Chemistry. Tentative RuIes for Section X. Natural Products and Related Compounds. In preparation. 16. International Union of Pure and Applied Chemistry, Section on Clinical Chemistry, Commission on Quantities and Units & International Federation for Clinical Chemistry, Committee on Standards, Expert Panel o n Quantities and Units. Quantities and units in clinical chemistry. Recommendation 1973. Pure appl. Chem. 37, 517, 1974. 17. International Union of Pure and Applied Chemistry, Section on Clinical Chemistry, Commission on Quantities and Units & International Federation for Clinical Chemistry, Committee on Standards, Expert Panel on Quantities and Units. List of quantities in clinical chemistry. Recommendation 1973. Pure appl. Chem. 37, 547, 1974. 18. Krupp, M. A., Sweet, N. J., Jawetz, E. & Biglien, E. G. Physician’s Handbook, 15th ed. Blackwell Scientific Pulblications, Oxford and Edinburgh, 1968. 19. McGlashan, M. L. Physicochemical Quantities and Units, 2nd ed. The Royal Institute of Chemistry, London, 197 1. 20. National Physical Laboratory. SI, The International System of Units. Her Majesty’s Stationery Office, London, 1970. 21. Richterich, R. Ktinische Chemie, Theorie und Praxis, 2nd ed. Akademische Verlagsgesellschaft, Frankfurt a.M., 1968. 22. Sjoblom, C. G. & Sundberg, B. Reagensboken, Beredning av Reagens pd Apotek. Svenska Bokforlaget, 1969. 23. Stadie, W. C. A method for the determination of methemoglobin in blood. J. biol. Chem. 41, 237, 1920. 24. van Kampen, E. J. & Zijlstra, W. G. Standardization of hemoglobinometry. 11. The hemiglobincyanide method. Clin. chim. Acta 6, 538, 1961. 25. v. Klein-Wisenberg, A. in de Boroviczhy, C. G. (ed.)Standardization in Haematology 111. S. Karger, Basel, New York, 1966; also in Bibl. haemat. (Basel) 24, 150, 1966.
26. World Health Organization. Cumulative List No. 3 of Proposed International Nonproprietary Names f o r Pharmaceutical Substances. Lists 1-25 published in World Health Organization Chronicle, nos. 7-25 (1 953-1 9 1 ) , World Health Organization, Geneva, 197 1. 27. World Health Organization, Expert Committee o n Specifications for Pharmaceutical Preparations. pp. XXXTI, XXXIV in Specifications f o r the Quality Control o f Pharmaceutical Preparations. International Pharmacopoeia, 2nd ed. World Health Organization, Geneva, 1967.
