Determination of Residual Solvents by Analytical Methods
MCOPS, Manipal ANALYTICAL METHODS FOR RESIDUAL SOLVENTS
INTRODUCTION:
Organic solvents are routinely applied during synthesis of drug substances, excipients, or during drug product formulation. They are not desirable in the final product, mainly because of their toxicity, their influence on the quality of crystals of the drug substance and their odor or taste, which can be unpleasant for patients. To remove them, various manufacturing processes or techniques (usually under increased temperature or/and decreased pressure) are in use. Even after such processes, some solvents still remain, yet in small quantities. These small quantities of organic solvents are commonly known as organic volatile impurities (OVIs) or residual solvents (RS).
In the early 80s, the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human use (ICH) was established. Then, in late 80is, RS were classified as impurities. Categories of residual solvents were presented in the preceding paper.
The ICH Harmonized Guidelines set up by the EU, Japan and USA for the registration of pharmaceutical products require, under ICH Topic Q3C (published in December 1997), for testing to be performed for residual solvents when production or purification processes are known to result in the presence of such solvents.
These guidelines set criteria for analytical methods used to identify and quantify these residual solvents as well provide acceptable concentration limits. USP has finally adopted the ICH Q3C guidelines set and has revised its general methods to reflect it. The new general chapter states what ICH Q3C contains, and in addition describes analytical methods for performing RS testing. Limits and different methods for determination of RS have been finally integrated in USP (1).
Methods accepted by pharmacopoeias and ICH Guidelines * The first analytical method for RS, which was published in pharmacopoeias,
INTRODUCTION:
Organic solvents are routinely applied during synthesis of drug substances, excipients, or during drug product formulation. They are not desirable in the final product, mainly because of their toxicity, their influence on the quality of crystals of the drug substance and their odor or taste, which can be unpleasant for patients. To remove them, various manufacturing processes or techniques (usually under increased temperature or/and decreased pressure) are in use. Even after such processes, some solvents still remain, yet in small quantities. These small quantities of organic solvents are commonly known as organic volatile impurities (OVIs) or residual solvents (RS).
In the early 80s, the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human use (ICH) was established. Then, in late 80is, RS were classified as impurities. Categories of residual solvents were presented in the preceding paper.
The ICH Harmonized Guidelines set up by the EU, Japan and USA for the registration of pharmaceutical products require, under ICH Topic Q3C (published in December 1997), for testing to be performed for residual solvents when production or purification processes are known to result in the presence of such solvents.
These guidelines set criteria for analytical methods used to identify and quantify these residual solvents as well provide acceptable concentration limits. USP has finally adopted the ICH Q3C guidelines set and has revised its general methods to reflect it. The new general chapter states what ICH Q3C contains, and in addition describes analytical methods for performing RS testing. Limits and different methods for determination of RS have been finally integrated in USP (1).
Methods accepted by pharmacopoeias and ICH Guidelines * The first analytical method for RS, which was published in pharmacopoeias,
References: 1. Bauer M., BarthElEmy C.: Handbook of solvents, Wypych G. Ed., 1st edn., p. 1129, ChemTec Publishing, Toronto, New York 2001. 2. http://www.pharmaquality.com/LabNotebook8.html 3. Acta Poloniae Pharmaceutica n Drug Research, Vol. 67 No. 1 pp. 13n26, 2010 4. XXXI USP, <467> General Chapter, Organic Volatile Impurities. 5. European Pharmacopoeia 6th Edition , 2.4.24. Identification and control of residual solvents. 6. Chen T. K., Phillips J. G., Durr W.: J.Chromatogr. A 811, 145 (1988).