Pharmaceuticals substance specific

IEC continues to have numerous applications to the detection and quantification of various inorganic ions.1 1 This is particularly true in water analysis.5-14 Inorganic ions in a variety of other sample types, such as food and beverages,1518 rocks,19-23 biological fluids, (blood, urine, etc.),24-31 pharmaceutical substances,32 33 concentrated acids,34 alcohols,35 and cleanroom air36 have also been analyzed by IEC. IEC has also been employed in isotopic separation of ions,37 including the production of radioisotopes for therapeutic purposes.3839 Typical IEC sample matrices are complex, and may contain substances that interfere with measurement of the ion(s) of interest. The low detection limits required for many IEC separations demand simple extraction procedures and small volumes to avoid over-dilution. Careful choice and manipulation of the eluent(s) may be needed to achieve the desired specificity, especially when multiple ions are to be determined in a single sample. 

These above mentioned errors would be discussed briefly here with specific examples. It is pertinent to mention here that errors outside the range of permissible errors in the analyses of pharmaceutical substances may cause serious problems because most of these substances are usually highly toxic, potent and used extensively in life-saving processes across the globe. 

As pharmacological activity is intimately related to molecular configuration, hence determination of specific rotation of pharmaceutical substances offer a vital means of ensuring their optical purity. 

Loss on drying reflects the net weight of a pharmaceutical substance being dried at a specified temperature either at an atmospheric or under reduced pressure for a stipulated duration with a specific quantity of the... 

In fact, certain known impurities are present in a number of pharmaceutical substances. The presence of such impurities may be carried out by performing prescribed specific tests in various official compendia in order to ascertain their presence within the stipulated limits. 

The errors that are solely attributed to sampling, specifically in the instance of heterogeneous solids, usually give rise to the most important source of uncertainty in carrying out analysis of pharmaceutical substances. 

Gravimetric analysis is an unique technique by means of which either an element or a compound is obtained in its purest form through isolation and subsequent weighing. In order to achieve this, the element or compound is first and foremost separated from a specific portion of the pharmaceutical substance being determined and consequently the weight of the constituent in the given sample is calculated on the basis of the weight of the product. 

In certain specific cases either the pure pharmaceutical substance or dosage forms are quantitatively converted to free compound. This conversion to free compound is quantitative and hence forms the basis of gravimetric analysis. A few typical examples belonging to this category are, namely progesterone suspension sterile, progesterone tablets, sodium lauryl sulphate, mephobarbital tablets and sorbitan monooleate. 

A plethora of chemical compounds for the determination of small amounts of water present in organic solids, pharmaceutical substances and organic solvents have been devised over a length of time. But unquestionably the most important of these is the one proposed by Karl Fischer (1935), which is considered to be relatively specific for water. It essentially makes use of the Karl Fischer reagent which is composed of iodine, sulphur dioxide, pyridine and methanol. 

Determination of specific optical rotation of pharmaceutical substances... 

The two characteristic parameters related to optical activity of the pharmaceutical substances, namely (a) optical rotation, and (b) specific optical rotation, can be measured satisfactorily by the help of a Polarimeter as stated below ... 

DETERMINATION OF SPECIFIC OPTICAL ROTATION OF PHARMACEUTICAL SUBSTANCES... 

The specific optical rotation of a large number of potent pharmaceutical substances may be determined by the above mentioned procedure but specific concentrations and method of preparation of solutions is according to the official compendium as stated in Table 19.2 below ... 

It is however, pertinent to mention here that most pure pharmaceutical substances possess a characteristic value of E (1% 1-cm) at a specific wavelength in agiven spectroscopic-grade solvent (UVASOL(R)-Mcrck). This particular property is the basis for most assay methods included in pharmacopoeia that are absolutely free from interfering materials, besides being utilized for identifying substances. 

The fingerprint region lies between 1300-400 cm-1 which is considered to be the most valuable component of the spectra and mainly comprises of a specifically large number of unassigned vibrations. Therefore, IR-spectroscopy aids in the identification of unknown compound by comparing its spectrum with a standard spectra recorded under exactly similar experimental parameters. Thus, pharmaceutical substances that exhibit the same infrared spectra may be inferred as identical. 

To identify the presence of undesirable specific organic compounds present as impurities in a number of pharmaceutical substances, namely morphine in apomorphine hydrochloride hydrazine in carbidopa 3-aminopropanol in dexampanthenol etc.,... 

A number of other typical examples of pharmaceutical substances containing specific organic compounds, that may be identified by adopting the similar TLC technique are stated in Table 28.3 ... 

Table 28.3 Cognate Assays of Specific Organic Compounds Present in Pharmaceutical Substances...

The size-exclusion-chromatography may be used for two specific purposes in the analysis of pharmaceutical substances, such as ... 

Part—IV has been entirely devoted to various Optical Methods that find their legitimate recognition in the arsenal of pharmaceutical analytical techniques and have been spread over nine chapters. Refractometry (Chapter 18) deals with refractive index, refractivity, critical micelle concentration (CMC) of various important substances. Polarimetry (Chapter 19) describes optical rotation and specific optical rotation of important pharmaceutical substances. Nephelometry and turbidimetry (Chapter 20) have been treated with sufficient detail with typical examples of chloroetracyclin, sulphate and phosphate ions. Ultraviolet and absorption spectrophotometry (Chapter 21) have been discussed with adequate depth and with regard to various vital theoretical considerations, single-beam and double-beam spectrophotometers besides typical examples amoxycillin trihydrate, folic acid, glyceryl trinitrate tablets and stilbosterol. Infrared spectrophotometry (IR) (Chapter 22) essentially deals with a brief introduction of group-frequency... 

Many thousands of pharmaceutical substances are routinely manufactured by the pharmaceutical industry. Two of the most important determinants of final product safety and efficacy are (a) the standard of raw materials used in the manufacturing process and (b) the standard (i.e. specification) to which the final product is manufactured. Most pharmaceutical substances are... 

World Health Organization (WHO) (2003), The International Pharmacopoeia, Tests and General Requirements for Dosage Forms Quality Specifications for Pharmaceutical Substances and Tablets, 3rd ed., Vol. 5, WHO, Geneva. 

Method validations and drug substance or finished pharmaceutical product specifications are intimately linked. To ensure transferability of the method and to ensure the method will operate successfully in a QC site, the method variation (from the intermediate precision) should be known and monitored. The method variation is an estimate of the variation that will be experienced in routine use of the method. More method variation will create unacceptable random failure rates, and provide no room for reasonable product variation or even minor stability changes. The method variation should be less than one-third of the interval from the mean or target (typically the midpoint of the upper and lower specification limit) value to the nearest specification limit, or one-sixth... 

It must be recalled that the World Health Organization (WHO) perceived the International Pharmacopoeia as a means of harmonizing quality specifications of pharmaceutical substances internationally. As long as WHO efforts are not given any legal status per se as they are, at best, mere recommendations, then other steps have to be found to affirm quality. It must be stated however that in 1981 the WHO Expert Committee on Specifications for Pharmaceutical Preparations reviewed the whole system and came out with its Twenty-Eight Report with clearly defined functions and characteristics of the International Pharmacopoeia. 

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