Diazotization titrations in pharmacopoeial quality control of medicines and proposals for their revision in the European Pharmacopoeia.

Based on the data in the Ph. Eur., some other newer pharmacopoeias and published experimental papers propose to revise the text of Ph. Eur. 2.5.8. First, it is necessary to specify which of the electrometric methods should be used to indicate the endpoint of diazotization titrations in Ph. Eur. (preferable potentiometry with a platinum indicating electrode). The amount of potassium bromide in the titration solution may be reduced to 1 g, the cooling of the solution before titration may be omitted from the framework procedure, and it may be specified in individual monographs if necessary to obtain accurate and correct results for some medicines. Diazotization titration can be performed in Ph. Eur. and can also be used to determine the content of some other medicines.

Colour and content of some metals in honey.

The paper highlights the correlations between the results of instrumental colour measurement and the content of certain metals in kinds of honey. Sufficiently close correlations may lead to the development of procedures for the rapid determination of the content of these metals in honey by colour measurement without the need for more demanding sample preparation.

Colour and content of some biologically active substances in honey.

This paper highlights the correlations between instrumental measurements of colour and the content of some biologically active organic compounds (especially phenolics and flavonoids) in honey. Sufficiently close correlations may lead to the development of procedures for rapid determination of the content of these substances in honey by colour measurement without the need for more demanding sample preparation.

Colour and antioxidant activity of honey.

The paper highlights the relationships between the results of instrumental colour measurement and the results of the determination of the antioxidant activity of honey (especially by DPPH and FRAP). The sufficiently close correlations show that once verified, supplemented by regression analysis and calibration, they may find application in the rapid determination of the antioxidant activity of honey.

Colour and content of some biologically active substances in natural products and products of natural origin.

The paper draws attention to the correlations between the results of instrumental colour measurements and the content of some biologically active organic substances (carotenoids, chlorophyll, anthocyanins, curcuminoids, etc.) in natural products and products of natural origin. After supplementation by regression analysis and calibration, sufficiently close correlations can lead to the development of procedures for rapid determination of the content of these substances and their groups by colour measurement without more demanding sample treatment.

Advances in the use of instrumental measurement of colour in the development, production and quality control of drugs, medicinal preparations and pharmaceutical auxiliary substances III.

Colour is an important indicator of the quality of pharmaceuticals, medicinal products and pharmaceutical excipients. The paper summarizes advances in the use of instrumental colour measurement in synthetic medicines and medicines of non-natural origin, their dosage forms and excipients published in 2013-2019.

Theory and practice of pharmacopoeial control of quality of drugs and excipients X. Number of parallel determinations, processing of results and their use in the assessment of the content of active substances and excipients in the European Pharmacopoeia (Ph. Eur.).

In the European Pharmacopoeia (Ph. Eur.) there is no prescribed number of parallel determinations of the content of active substances and excipients. The authors suggest adding at least three determinations. The results of parallel determinations suggest to test for outliers before using test based on the ratio of the range of results (p = 0.95) and not to compare individual results with the tolerance limits given in Ph. Eur., but with their arithmetic mean. Furthermore, they propose to extend the Chapter 5.3. of the European Pharmacopoeia so as to be applicable not only to bioassays, but also to chemical, physicochemical and physical assays and tests, starting with the content of active substances and excipients.

Theory and practice of pharmacopoeial control of quality of drugs and excipients IX. The problem of tolerance limits for the content of active substances and excipients in the European Pharmacopoeia (Ph. Eur.).

Content tolerance limits should respect the acceptable variation in the content of the active substance or excipient from its production and the variability of the results of the analytical procedure prescribed to determine the content by the appropriate pharmacopoeia. This usually prevails in the active substances and excipients. They should be derived statistically based on the precision of the prescribed analytical method determined by the interlaboratory test. Calculations from published precision characteristics show that some tolerance intervals for the active substance content are probably too narrow in Ph. Eur. This can lead to erroneous decisions about their quality.

Theory and practice of pharmacopoeial control of quality of drugs and excipients VIII. End-point indication and other conditions for the titration of primary aromatic amines in the European Pharmacopoeia (Ph. Eur.).

Indication of the equivalence point for the titration of primary aromatic amines (sulphonamides, etc.) with sodium nitrite solution according to Ph. Eur. (2.5.8) is performed electrometrically or using a prescribed indicator, the electrometric method not being specified. Better reproducibility of the assay results would add to Ph. Eur. the electrometric method to be used for the indication and suitable electrodes for it. The authors of the paper propose a potentiometric indication, which is in Ph. Eur. widely used. Further, they propose to consider whether in Article 2.5.8. Ph. Eur. indications using an indicator as an alternative to the instrumental indication required. The titration in the presence of hydrochloric acid favourably affects the addition of potassium bromide, cooling the solution prior to the titration prescribed by Ph. Eur. is not needed.

On the content of the National part of the Czech Pharmacopoeia 2017.

This paper deals with the content of the national part of the Czech Pharmacopoeia (CP) 2017 in terms of preparation of pharmaceuticals in pharmacies, quantitative methods for controlling their quality and their usable life. Despite the longer time span of the CP 2017 since the CP 2009, compared to the CP 2009 from the CP 2005, the content of the CP 2017 can not be evaluated as a more pronounced shift from the national part of the CP 2009. Some issues of the national section of the CP 2017 are discussed in detail in the paper. Key words: Czech Pharmacopoeia 2017 • content of the national part • preparation of medicinal products in pharmacies.

Theory and practice of pharmacopoeial control of the quality of drugs and excipients VII. The colour reference solutions of the European pharmacopoeia (Ph. Eur.).

Data calculations of three different workplaces consistently show that the difference in colour ΔE (CIELAB) of some colour reference solutions according to Ph. Eur. with small colour and purified water are too small. As a result, there is failure with use of these solutions for visual assessment of the coloration of the liquids. Solving the problem in Ph. Eur. presupposes the introduction of instrumental colour evaluation into this pharmacopoeia. Key words: Ph. Eur. • colour reference solutions • colour difference • CIELAB • visual assessment • instrumental measurement.

[Advances in the use of instrumental measurement of colour in the development, production and quality control of drugs, medicinal preparations and pharmaceutical auxiliary substances II*]. / Pokroky ve vyuzití instrumentálního merení barevnosti ve vývoji, výrobe a v kontrole jakosti léciv, lécivých prípravku a farmaceutických pomocných látek II*

The paper summarizes the use of instrumental colour measurement in the field of pharmaceuticals of natural origin and other substances of natural origin beneficial for health in recent 10 years. Colour measurement in this field was most frequently employed in the monitoring of various aspects of the process of drying of medicinal plants and their parts.

[Standard prescriptions for extemporaneously produced medicinal preparations in pharmacies VI. Collection Neues Rezeptur-Formularium]. / Standardní receptura pro prípravu lécivých prípravku v lékárnách VI. Sbírka Neues Rezeptur-Formularium*

The paper deals with the content of the collection Neues Rezeptur-Formularium (NRF) and some prescriptions potentially usable in innovations and standardization of prescriptions for extemporaneously produced medicinal preparations in pharmacies in the Czech Republic. Another possible use of NRF in the Czech Republic consists in the revision of the National Section of the Czech Pharmacopoeia.

[Advances in the use of instrumental measurement of colour in the development, production and quality control of drugs, medicinal preparations and pharmaceutical auxiliary substances I ]. / Pokroky ve vyuzití instrumentálního merení barevnosti ve vývoji, výrobe a v kontrole jakosti léciv, lécivých prípravku a farmaceutických pomocných látek I

Colour is one of the important indices of the quality of drugs, medicinal preparations and pharmaceutical auxiliary substances. The paper summarizes the development and use of instrumental measurement of colour in pharmacy in recent ten years focusing on the drugs of synthetic origin and pharmaceutical auxiliary substances including their control.

[Standard prescriptions for the formulation of medicinal preparations in pharmacies V. The collection Dermatologische Magistralrezepturen der Schweiz]. / Standardní receptura pro prípravu lécivých prípravku v lékárnách V. Sbírka Dermatologische Magistralrezepturen der Schweiz.

The paper deals with the content of the collection Dermatologische Magistralrezepturen der Schweiz (DEMARES) and the prescriptions from this collection which can be potentially usable in the innovations and standardization of the prescriptions of dermatologic medicinal preparations formulated in pharmacies in the Czech Republic. Another possible use of the collection DEMARES is for the revision of the National Section of the Czech Pharmacopoeia.