Standard international units

A subsection on Clinical Laboratory Evaluations is to describe changes in patterns of laboratory tests with drug candidate use. As mentioned earlier, marked laboratory abnormalities and those that led to a substantial intervention are to be reported in the subsection on SAEs. The appropriate evaluations of laboratory values will usually be determined by the results observed and should include comparison of the treatment and control groups. Normal laboratory ranges, given in standard international units, should be provided for each analyte measured. A brief overview of the major changes in laboratory data (e.g., hematology, clinical chemistry, urinalysis, and other data as appropriate) at each time (e.g., at each clinical visit) over the course of the studies should include information on... 

Menotropins are a natural product that is obtained from the urine of postmenopausal women and then biologically standardized (International units [lU]) for FSH and LH activities in an approximate ratio of 1 1. Menotropins are used in males with primary (hypothalamic) or secondary (pituitary) hypogonadism to stimulate spermatogenesis, providing they have been treated previously with human chorionic gonadotropin (hCG a peptide hormone of placental origin that has activity very similar to LH discussed below) to effect masculinization (increased testosterone... 

One standard international unit (1 lU) is the quantity of enzyme that catalyzes the conversion of 1 micromole (pmol) of substrate per minute under specified reaction conditions. Thus, unlike the turnover number, which is a constant characteristic for one molecule of a particular enzyme, international units measure how much enzyme is present. For example, an enzyme preparation with an activity corresponding to 40 lU contains a concentration of enzyme 40 times greater than the standard. This is a useful way to measure enzyme activity because the level of enzyme activity compared with normal activity is significant in the diagnosis of many diseases (Section 10.9). 

As already stated above, the peroxide value is also expressed in other units milliequivalent of active oxygen per kg, millimol of active oxygen per kg or mg of active oxygen per kg. These units may be converted into mmol of active oxygen per 2 kg (Standard International Units), using the following factors ... 

OSTL optically stimulated llieimoluiiiinesceiice SIU standard international units... 

In underwater acoustics, the metric system has not been universally applied, and a number of nonmetric units are stOlused distances of nautical rmles (1852 m), yards (0.9144 m), and kiloyards speeds of knots (nautical miles per hour) depths of fathoms (6 feet or 1.8288 m) and bearing in degrees (0.01745 rad). In the past two decades, however, there has been a conscious effort to become totally metric, that is, to use meter-kilogram second (MKS) or Standard International units. 

Before pure vitamin A was available for chemical analysis, the vitamin A content of foods was determined by biological assays, and the results expressed in standardized international units (iu) 1 iu = 0.3 fig retinol, or 1 fig of retinol = 3.33 iu. Although obsolete, international units are sometimes still used in food labelling. 

In 1949 the World Health Organization adopted the biological activity of 1 mg of an oil solution containing 0.025 p.g of crystalline D as the analytical standard for vitamin D. This standard was discontinued in 1972. USP uses crystalline cholecalciferol as a standard (80). Samples of reference standard may be purchased from U.S. Pharmacopeia Convention, Inc., Reference Standards Order Department, 12601, Twinbrook Parkway, Rockville, Maryland 20852. One international unit of vitamin D activity is that activity demonstrated by 0.025 ]1 of pure crystalline (7 -vitamin D. One gram of vitamin D3 is equivalent to 40 x 10 lU or USP units. The international chick unit (ICU) is identical to the USP unit. 

The roentgen is the international unit of quantity for both x-rays and y-rays. It is the quantity of this radiation which will produce, as a, result of ionization, one electrostatic unit of charge, of either sign, in one cubic centimeter of dry air (as measured at 0° C and standard atmospheric pressure). 

In each of tiie assays of potency the amount of the immunosenim and the amount of a corresponding standard antitoxin dial are required to neutralize die effects of a defined dose of the corresponding toxin are determined. The two determined amounts and die assigned unitage of the standard antitoxin are dien used to calculate the potency of die immunoserum in International Units (lU). 

The procedure employed for the establishment of the chemical reference substances used in these assays has been previously published (Sandrin et al. 1997). The CRSs for the microbiological assays of antibiotics are first submitted to the chemical tests of the monograph. If the results are satisfactory, a collaborative microbiological assay is carried out, using the International Standard as calibrator. Thus, these reference substances are considered to be secondary reference substances since they are calibrated against existing standards. Potency is expressed in International Units. If an International Standard does not exist, European Pharmacopoeia Units are used. 

In addition to KM and vmax, the turnover number (molar activity) and the specific activity are two important parameters in enzyme catalyzed reactions. The turnover number indicates the number of substrate molecules converted per unit time by a single enzyme molecule. The specific activity is given in units and one international unit (i.u.) is the amount of enzyme that consumes or forms 1 pmol of substrate or 1 pmol of product per minute under standard conditions. 

The potency of interferon-a2 is estimated by comparing its effect to protect cells against a viral cytopathic effect with the same effect of the appropriate International Standard of human recombinant interferon-a2 or of a reference standard calibrated in International Units. 

The International Unit is the activity contained in a stated amount of the appropriate International Standard. The equivalence in International Units of the International Standard is stated by the World Health Organization. 

From time to time, probably all science students find themselves entangled in a problem of units. For those who have advanced through physical chemistry to the level of this book, these problems have obviously not been insurmountable. It is likely, however, that —along with feelings of frustration—these students have been left with the wish that everyone used the same units, specifically those units with which they are most comfortable. In response to the recognized need for uniformity, IUPAC recommends the use of Systeme international d unites (International System of Units, SI) units, which are essentially standardized mks units. 

Turnover numbers can be measured only when the concentration of the enzyme is known. Partly for this reason the activity of an enzyme is usually given as specific activity, the units of activity per milligram of protein. One international unit is the amount of enzyme that produces 1 prnol of product per minute under standard (usually optimal) conditions. The International Union of Biochemistry17 has recommended a larger unit, the katal (kat), the amount of enzyme that converts one mol s 1 of substrate to product. 

The actual molar concentration of an enzyme in a cell-free extract or purified preparation is seldom known. Only if the enzyme is available in a pure crystalline form, carefully weighed, and dissolved in a solvent can the actual molar concentration be accurately known. It is, however, possible to develop a precise and accurate assay for enzyme activity. Consequently, the amount of a specific enzyme present in solution is most often expressed in units of activity. Three units are in common use, the international unit (IU), the katal, and specific activity. The International Union of Biochemistry Commission on Enzymes has recommended the use of a standard unit, the international unit, or just unit, of enzyme activity. One IU of enzyme corresponds to the amount that catalyzes the transformation of 1 p,mole of substrate to product per minute under specified conditions of pH, temperature, ionic strength, and substrate concentration. If a solution containing... 

These differences in biopotency are reflected in the standardization of the vitamin in terms of international units (iu). An international unit is equivalent... 

The differences between the units can be ignored when the exact numerical values are not under consideration, unless otherwise we need the nature of activation volumes in order to obtain some aspects of the reaction mechanism, e.g., 1 kbar = 100 MPa = 1000 kg/cm2 = 1000 atm = 7.5 x 105 mmHg. This is indeed the case in high-pressure synthetic chemistry or preparation under pressure. In the Systeme International d Unites (SI units) adopted by the Conference Generale des Poids et Mesures and endorsed by the International Organization for Standardization, the unit of force is the Newton (N), which is equal to kilogram x (meter per second) per second and is written as kgm s 2. The SI unit of pressure is one Newton per square meter (Nm 2) which is called a Pascal (Pa) 1 bar = 105 Pa thus, the Pa is used in this chapter as an approximate equivalent to other units (Table 1). 

Vitamin A or a precursor must be provided in the diet. This vitamin occurs in various forms (vitamers) retinol (alcohol), retinal (aldehyde), retinoic acid and vitamin A palmitate (ester). Requirements for vitamin A are usually expressed in international units (IU) per kg of diet. The international standards for... 

The original reference standard of vitamin D was a solution of irradiated ergosterol in olive oil. The present international standard is a solution of pure crystalline cholecalciferol in olive oil containing 0.025 pg/mg of solution. One international unit (IU) is equivalent to 0.025 pg of crystalline D3 or 1 pg of D3 is equivalent to 40 IU. The USP reference standards are crystalline ergocalciferol or cholecalciferol packaged in sealed ampules. The USP standards and the international standards are equivalent in that 1 pg of each is equivalent to 40 IU. 

True quantification of pyrazines in the powdered sarples presented seme difficulty. Due to sensitivity problems in sampling reconstituted sairples, the decision was made to purge the powdered NFCM. An internal standard could not be easily added to a dry sample, so quantification was accomplished calculating concentrations relative to response factors determined for external standard solutions. Standardized concentration units were determined using the following relationships ... 

An international standard for hyaluionidase was accepted in 1957 by the World Health Organization (WHO) [131]. This was of gnat historical value, since hyaluronidase is one of the fust biological international standard reference preparations ever made. The International Unit (IU) was and is still defined as the activity of 0.1 mg of the International Standard Preparation. It is recommended that the standard be employed for the assay of hyaluronidase from testicular origin (RC.3.2.1.35). According to the WHO, the standard should be valid for all methods of comparison, including turbidimetric and visco si metric assays. The first international WHO standard 1955 hyaluionidase is still available in tablet form with an activity of approximately 200 IU per tablet... 

The Jhtemationai Union of Biochemistry (TUB) was officially founded in 1953 by an initiative of the British Biochemical Society. At ibis time enzyme standardization was in a chaotic slate, owing to the multiplicity of arbitrarily defined units of enzyme activity and the ilt-dtfned nomenclature. In 1955, the 1UB International Commission on Enzymes was created. This led to an improved enzyme nomoidature, which has been used since 1961, and the definition of the International Unit (LU.) of enzyme activity. 

Because of the lack of an international standardization of units, Table 1.44 provides some conversion factors among the various units used in defining the process properties of H2. 

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