United States Pharmacopoeia

The 2000 U.S. Pharmacopoeia and National Formulary, USP 24-NF 19, was published in October 1999. It became official on 01.01.2000. USP-NF is one of, if not the most, widely recognized of the world s pharmacopoeial compendia of standards for drug strength, quality, purity, packaging, labelling and storage. USP-NF also provides standards for devices and diagnostics, as well as nutritional supplements. 

USP-NF Supplements are published twice a year. They contain all the approved changes to USP-NF Monographs and General Chapters as well as newly adopted monographs. 

The Pharmacopoeial Forum fulfills a vital role in promoting industry-wide communication between those involved with quality assurance, the development of standards and analytical methods. It contains an up to date list of official USP Reference Substances, with current and recently changed lot numbers. Reference Substances not yet available and those under development are also described. The publication acts as an international open forum in which scientists are invited to express their views, suggestions, ideas and comments regarding new drug standard development and revisions to existing monographs. Pharmacopoeial Forum is published, on a subscription basis, six times a year, back issues are available for USP website see Table 84. 

The EP is published under the direction of the Council of Europe and is available in English and French. It is the result of obligations undertaken in a convention set up under the auspices of the Council of Europe and signed by 19 countries. The EP has two important aspects, the unification of national pharmacopoeia and the unification of methods of quality control of medicines. 

Pharmeuropa is available by annual subscription in English and Frendi from the Council of Europe and is published four times per year. Like the U SP s Pharmacopoeial Forum it contains draft monographs for comment, official announcements, scientific notes and the contents to the fascicles issued by the EP for EP website see Table 8.4. 

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The fermentation-derived food-grade product is sold in 50, 80, and 88% concentrations the other grades are available in 50 and 88% concentrations. The food-grade product meets the Vood Chemicals Codex III and the pharmaceutical grade meets the FCC and the United States Pharmacopoeia XK specifications (7). Other lactic acid derivatives such as salts and esters are also available in weU-estabhshed product specifications. Standard analytical methods such as titration and Hquid chromatography can be used to determine lactic acid, and other gravimetric and specific tests are used to detect impurities for the product specifications. A standard titration method neutralizes the acid with sodium hydroxide and then back-titrates the acid. An older standard quantitative method for determination of lactic acid was based on oxidation by potassium permanganate to acetaldehyde, which is absorbed in sodium bisulfite and titrated iodometricaHy. 

Test Methods. In addition to that provided by proper sampling and rephcation of analysis, a test method also has a significant impact on the accuracy and precision of the results. Preferred methods are those which are accepted in the chemical industry such as those from the American Society of Testing Materials (ASTM), Association of Official Analytical Chemists (AO AC), or from compendia such as the United States Pharmacopoeia (USP) or the Pood Chemical Codex (FCC) (36). The use of such methods eliminates the need for method vahdation. 

There are a variety of analytical methods commonly used for the characterization of neat soap and bar soaps. Many of these methods have been pubUshed as official methods by the American Oil Chemists Society (29). Additionally, many analysts choose United States Pharmacopoeia (USP), British Pharmacopoeia (BP), or Pood Chemical Codex (FCC) methods. These methods tend to be colorimetric, potentiometric, or titrametric procedures. However, a variety of instmmental techniques are also frequendy utilized, eg, gas chromatography, high performance Hquid chromatography, nuclear magnetic resonance spectroscopy, infrared spectroscopy, and mass spectrometry. 

An entirely different type of contamination arises from the presence of microbiota in a product. As in the case of chemical contamination, compendial requirements for microbiological purity exists. Pharmacopoeial standards vary from country to country, and manufacturers must use the specifications and kill times that meet local requirements. As of this writing, the criteria in the British Pharmacopoeia are more stringent than those estabUshed by the CTFA, which are stricter than those in the United States Pharmacopoeia. In order to meet commonly accepted standards of microbial purity, manufacturing faciUties must be periodically cleaned and all products that can support microbial growth must contain an effective preservative (6). 

The British Pharmacopoeia (1932) recognises three of these solanaceous drugs and specifies for them minimum requirements per cent, of total alkaloids, calculated as hyoscyamine, viz. belladonna, leaves 0-3, root 0-4 henbane, leaves and flowering tops 0-05 stramonium, leaves and flowering tops 0-25. The United States Pharmacopoeia, XIII, specifies the same minimum limits for belladonna leaves and stramonium and for henbane, 0-04. 

A method for the estimation of the total alkaloids and of non-phenolic alkaloids (emetine fraction) is given in the British Pharmacopoeia, 1932, Addendum VI, which requires the drug to contain not less than 2 per cent, of alkaloids, of which at least 55 per cent, must be non-phenolic bases, calculated as emetine. The British Pharmacopoeia also gives an assay process for emetine in emetine bismuth iodide, the form in which the drug is chiefly used in medicine it is required to contain not less than 25 and not more than 28 per cent, of emetine. In the United States Pharmacopoeia, XIII, both Cephcelis Ipecacuanha and C. acuminata are recognised and must contain not less than 2 per cent, of ether-soluble alkaloids. 

Neither the drugs yielding these alkaloids nor the alkaloids themselves are now recognised in the British or United States Pharmacopoeia, but the drugs still appear in non-official publications along with veratrine, which may be either amorphous, i.e., the mixture already referred to, or crystalline, i.e., the alkaloid cevadine. 

Pharmacopoeia publications provide a final important source of information for the pharmaceutical industry, regulatory authorities, and the healthcare professions. These are concerned with establishing quality standards. These publications include monographs that define specifications for the purity and identity of established pharmaceutical ingredients, both active and non-active, together with recognised analytical methods that may be used to evaluate them. The most relevant are the United States Pharmacopoeia (USP) and the European Pharmacopoeia (Ph.Eur). 

Table 11.3 Specifications for United States Pharmacopoeia (USP) grade Purified Water and Water for Injection.

Turco S. Young R.E. (19S7) Sterile Dosage Forms, 3rd edn. Easton, Philadelphia Lea and Febiger. United States Pharmacopoeia (1995) 23rd revision. Rockville, MD US Pharmacopoeia Convention. 

However, the establishment of a new endotoxin standard by the World Health Organization is a recent example of successful international collaboration between the World Health Organization, the United Stated Pharmacopoeia and the European Pharmacopoeia (Poole et al. 1997). Thus this standard is available from any of these organizations to be employed as a reference in the harmonized Limulus Amoebocyte Lysate test. 

Exchanges between pharmacopoeias are co-ordinated by the Pharmacopoeial Discussion Group (PDG) (International Harmonisation 1995) and it is frequent that one pharmacopoeia participates in a collaborative study organized by another pharmacopoeia, or that several pharmacopoeias share the same batch of reference substance to be used in their respective monographs nevertheless, in this case the reference substance can not be considered as harmonized. A new batch of erythromycin was shared between the United States Pharmacopoeia and the European Pharmacopoeia and was established in a common coEaborative study both for the microbiological assay (used in the USP for formulations) and the liquid chromatographic assay (used in the Ph. Eur. and USP for bulk material). 

AO AC Technical Division on RMs United States Department of Defense United States Food and Drug Administration US Geological Survey United States Pharmacopoeia Valid Analytical Measurement, UK World Health Organization... 

Elderberries were listed in the United States Pharmacopoeia from 1820 to 1831 and the flowers from 1831 to 1905. Elder is still an official herb in the British Pharmacopoeia. Elder is grown on most German properties and the German Office of Health recommends elder flower tea for the treatment of colds with fever. 

The discussion will be restricted to those tests that are mandatory in The United States Pharmacopoeia (USP)... 

USP24. <601 > Aerosols, Metered Dose Inhalers, and Dry Powder Inhalers. The United States Pharmacopoeia and National Formulary 1895-1912, 2000. 

USP XXII < 1225 > (1990), United States Pharmacopoeia, Validation of compendial methods... 

United States Pharmacopoeia, United States Pharmaceutical Convention, Inc., Rockville, MD, 2003, p. 1112. 

For assaying oxytetracycline content in injections, tablets, capsules, ointments, and oral suspensions, the United States Pharmacopoeia 28 [1] uses a liquid chromatography method described in the assay under oxytetracycline. For oxytetracycline and Nystatin capsules and for oral suspension, United States Pharmacopoeia 28 [1] uses a microbiological method listed under antibiotics-microbial assays <81>. 

United States Pharmacopoeia 28 [1] describes a microbiological method under antibiotics-microbial assays for the analysis of OTC and nystatin capsules, OTC and nystatin for oral suspension, OTC HC1 and hydrocortisone ointment, and OTC HC1 and polymyxin B sulfate ointment. The methods are relative rather than absolute, which are based on the determination of the level of oxytetracycline by a microbiological response to a series of standard oxytetracycline concentrations by a... 

Ibrahim et al. [49] described a spectrophotometric method for the determination of primaquine and other antimalarial agents in pharmaceuticals. Powdered tablet or ampule contents containing 25 mg of primaquine phosphate, was dissolved in water and the solution was made alkaline with 6 M ammonia before extraction with chloroform. The extract was evaporated to dryness and the residue was dissolved in acetonitrile. A portion of the solution was mixed with 0.04% tetracyanoethylene solution in acetonitrile and diluted to volume with acetonitrile. After 10 min, the absorbance was measured at 415 nm for primaquine. Beer s law was obeyed from 2 to 12 mg/mL. The results agreed well with those of the United State Pharmacopoeia XX method. 

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