Suite j, linthicum, md 21090, usa keywords static headspace, residual solvents, usp abstract usp residual solvents 1 is a general chapter in the us pharmacopeia that describes a headspace gas. Because of the interference of some protein particles and their physical characteristics fragile or translucent, the results. The design of volumetric apparatus is an important factor. General notices general chapters dietary supplements chapters reagents reference tables dietary supplements nf monographs usp monographs chromatographic columns glossary contact usp usp home page technical support site email software tech support email customer service general chapters. Uspnf general chapter general chapter 467 is being revised in two ways. Buffer salts of requisite for compendial purposes, ph is defined as the value givenpurity can be obtained from the national institute of sci. All samples were prepared according to the usp general chapter methodology. Updated 15jun2007 this explanatory note is intended to inform users regarding upcoming revisions to general chapter 467 residual solventsorganic volatile impurities, the current status of the general notices requirements, and the current organic. The following nomenclature pertains to five general types of preparations, all of which are suitable for, and intended for, parenteral administration. Usp residual solventsapplying the agilent 5977a msd with.
The optimized procedures use a static headspace introduction system with a gas chromatograph equipped with a. Usp is divided into two separate sections based upon. Usp will then address the information in the individual monograph. Some alkaloids and other nitrogencontaining organic compounds fail to yield all of their nitrogen upon digestion with sulfuric acid.
Usp is divided into two separate sections based upon sample solubility. Analytical standards for usp residual solvents the usp general chapter residual solvents is a method widely used for identifying and quantifying residual solvents, when there is no information available on what solvents are likely to be present. The ira was published in pharmacopeial forum 333 and became official on june 1, 2007. Rewrite chapter 467 residual solvents a survey was conducted in the pharmaceutical industry during 20 on the use of the chapter and ways to improve and enhance it. The usp will then address this topic in the individual monograph. Buffer solutions for standardization 791 ph of the.
Where less than 10 ml of titrant is to be measured, a 10ml buret or a microburet generally is required. In general, solvents are not completely removed by practical manufacturing techniques. Revised usp chapter and its application to excipient. On july 1, 2008, the united states pharmacopeia usp implemented a new test requirement for the control of residual solvents in drug products usp 30 nf 25. The single calcudistribution practices for lated temperature at which the total amount of degrada tion over a particular period is equal to the sum of the. So, the results from the alternate method will have to be compared to the. This training will provide an overview of general chapter usp requirements for testing of residual solvents and limits, along with providing updates on the new content added to provide greater flexibility in testing compliance. The requirements, known as general chapter, replaced the previous usp general chapter designated under organic volatile impurities.
General chapter does not address solvents deliberately used as excipients nor does it address solvates. In anticipation, the us food and drug administration. Residual solvents1 the calculation results in a level equal to or below that pro. This nomenclature has been adopted by the usp drug nomenclature committee for implementation by supplemental revisions of usp 23nf 18. Because of its potential, it should be considered a viable technique for plasma spectrochemistry in the pharmaceutical laboratory. Refer to chapter of usp37nf32 s1 for further information and details on adjustments not shown. Standard solutions prepare, in the solvent specified in the monograph, solutions of the usp reference standard or designated substance having accurately known concentrations of 0. As part of an ongoing monograph modernization initiative, the united states pharmacopeial convention usp is updating general chapter impurities in drug substances and drug products 1086 and proposing this new chapter that addresses organic impurities testing for articles subject.
Optimization of the waterinsoluble procedures for usp. Significant revisions to standards for residual solvents found in general chapter of the united states pharmacopeia national formulary uspnf became official on july 1, 2008. Tests for residual solvents are not generally mentioned in. All substances and products are subject to relevant control of solvents likely to be present in a substance or product. Usp residual solvents adapting to the new requirements. Ppt interpretation of the new usp general chapter residual solvents chair. Residual solvents vided in this general chapter, no testing of the drug productfor residual solvents need be considered. A total of 6 commentssuggestions were received from 22 organizations. Coming july 2008, the new united states pharmacopoeia usp. Validation of compendial procedures general information usp 36 precision analytical performance characteristics definitionthe precision of an analytical procedure is the degree of agreement among individual test results when the procedure is applied repeatedly to multiple samplings of accuracy a homogeneous sample.
This test is usually used for determining the content of inorganic impurities in an organic substance. Pharmacopeia usp, testing of drug substances, excipients, and drug products for residual solvents should be performed when production or purification processes are known to result in the presence of such residual solvents. Until 2008, the usp limited and tested for only chloroform, dioxane, methylene chloride and trichloroethylene. Pressurebalanced headspace for the determination of class. Residual solvents abstract the united states pharmacopoeia usp has published in usp volume 30 that there will be a major revision to monograph effective july 1, 2008. Otherwise an appropriate validated procedure is to be employed. Residual solvents under usp 467 ich q3c guidelines.
Briefing 476 organic impurities in drug substances and drug products. The chapter now includes a comprehensive listing of the class i, ii. Proposed revision was published in pharmacopeial forum 41 5. Specific requirements for chromatographic procedures for drug substances and dosage forms, including adsorbent and developing solvents, are given in the individual monographs. In cases where the test load is different than the smallest net weight, the assessment of the. System was used for the analysis of usp residual solvents at their limit.
The usp monograph references procedures a and b for. Check statuscommentary 20200226 hmc website introduces new features statuscommentary under monographs. This chapter provides guidance on the measurement of size distributions of particles in any phase system e. Usp chapters and implementation strategy kahkashan zaidi usp. What are usps expectations relating to general chapter between now and july 1, 2008. Pdf optimization of the waterinsoluble procedures for. Current chapter title is 467 organic volatile impurities introduction. Other appropriate validated procedures are to be employed for the quanti. Good storage and shipping practices1 internationally harmonized documents intended to assist. Usp chapter delayed general chapter organic volatile impuritiesresidual solvents implementation date delayed to july 2008 in accordance with the rules and procedures of the council of experts, this revision bulletin changes the implementation date of the general notices statement on residual solvents from july 1, 2007, to july 1. Solvents provide no therapeutic benefit, therefor all residual solvents should be removed to the extent possible to meet product specifications, good manufacturing practices, or other qualitybased. The residue on ignition sulfated ash test utilizes a procedure to measure the amount of residual substance not volatilized from a sample when the sample is ignited in the presence of sulfuric acid according to the procedure described below. Analysis of usp method residual solvents on the agilent. In harmonization with the ich, the usp has changed the general chapter, which became effective july 1st, 2008.
This new requirement, known has a general chapter designated under residual solvents, replaced the previous usp general chapter designated under organic volatile. Residual solvents assessed in this general chapter are listed in appendix 1 by common names and structures. Understanding the revisions to usp monograph united states pharmacopoeia usp provided control limits and testing criteria for seven organic volatile impurities ovis. Acceptable exposure levels in this general chapter for class 2 residual solvents were established by calculation of pde values according to the procedures for setting exposure limits in pharmaceuticals page 5748 of pf 156 nov.
In 2008, the usp implemented new testing requirements for the control of residual solvents. A new solvent or revised limit that has been approved through the ich process will be added to the appropriate list in this general chapter. Optimization of the waterinsoluble procedures for usp general chapter residual solvents. Usp chapter 467 delayed general chapter 467 organic volatile impuritiesresidual solvents implementation date delayed to july 2008 in accordance with the rules and procedures of the council of experts, this revision bulletin changes the implementation date of the general notices statement on residual solvents from july 1, 2007, to july 1. The usp general chapter residual solvents applies to both human and veterinary drugs and to compendial and noncompendial drug products. First, a revised procedure for waterinsoluble articles became official through an interim revision announcement ira. The procedures described in the identification, control, and quantification of residual solvents section of this general chapter are to be applied wherever possible. Usp nf general chapter 467 residual solvents organic volatile impurities posting date. The waterinsoluble procedures in us pharmacopeia usp general chapter residual solvents, which are based on european pharmacopoeia procedures, were optimized and modified before their inclusion in the chapter to improve their scope, performance, and ruggedness. Revised usp chapter and its application to excipient qualification and testing sky countryman phenomenex inc. Chapter testing procedure for residual solvents will go into effect.
These changes have significant impact for the industry. Delete crossreferences to general chapter heavy metals from all. Because the standard deviation is virtually independent of sample mass within the balances capacity, use of a small test load, which may be difficult to handle, is not required. This chapter defines the terms and procedures used in chromatography and provides general information. The objective of this general chapter is to define acceptable amounts of residual solvents in pharmaceutical drug products and dietary supplement products for the safety of the patient. Note heat or sonication may be used to dissolve the drug substance where use of such does not adversely affect the compound. This general chapter applies to existing drug substances, excipients, and products. However, because libs is still an emerging technique, details will not be further discussed in this general chapter.
1645 1268 102 955 237 354 1194 1448 269 1491 1401 658 252 983 1595 246 1589 1355 189 1616 1106 73 194 168 817 621 1099 1210 580 129