Issue link: https://www.e-digitaleditions.com/i/1300450
22 BioPharm International eBook October 2020 www.biopharminternational.com process of assessing the suitabil- ity of a compendial analytical test procedure under the conditions of actual use may or may not require actual laboratory performance of each analytical performance char- acteristic. The degree and extent of the verification process may depend on the level of training and experience of 'user'." Pha r macopoeias a re complex doc uments that are not always well mapped out or consistent. A ny work i ng a na ly t ica l proce - du r e ne e d s to i nc lude a l l t he p h a r m a c o p e i a l e l e m e nt s . F o r e x a mple, how c a n a n a n a ly st i nte r p r e t a n i n s t r u c t io n i n a monog raph suc h a s "D r y ove r silica gel for 18 h" or "Dry for 3 hours at 105°" without knowing the applicable general chapters a nd t hei r i nterac t ion w it h t he G enera l Not ices? T he relat ion- s h ip s b e t we e n t he i nd iv id u a l steps in an inter preted method for LOD, General Chapter <731>, t he G e ne r a l N ot ic e s, a nd t he A LCOA+ requ irements a re out- lined in a later section. How many determinations? T he m e t he n a m i ne m a nd e l at e monograph, like all other mono- graphs, gives the requirement for a si ng le deter m i nat ion, wh ic h i s not u s u a l ly b e st a n a ly t ic a l prac t ice. However, t he General N o t i c e s , 7.10 c l e a r l y s t a t e s , "A na ly t ica l resu lts obser ved in the laboratory (or calculated from experimental measurements) are compared with stated acceptance criteria to determine whether the article conforms to compendial r e q u i r e me nt s . T he r e p o r t a b le value, which often is a summary value for several individual deter- minations, is compared with the acceptance criteria. The report- able value is the end result of a completed measurement proce- dure, as documented" (11). I n o t h e r w o r d s , t h e d o c u - m e nt e d a n a l y t i c a l p r o c e d u r e must include the replication to be adopted a nd t he met hod of calculating the reportable value must be explicitly defined. Monograph tests for methenamine mandelate As seen in Figure 3, the tests in the monograph to be performed for methenamine mandelate are: • Identification by IR spectroscopy • Assay by titrimetry • I mpu r it ies by obse r vat ion, gravimetry, and titrimetry • Water content by gravimetric analysis. The last three (assay, impurities, and water content) are classical analytical chemistry tests, which are usually performed manually, Regulatory Sourcebook Data Integrity Figure 2. Tests, General Chapters, and General Notices required from the United States Pharmacopeia (USP) Methenamine Mandelate Monograph. USP 42 (01-May-2019) MONOGRAPH (Legal Standard) TESTS & METHODS REQUIRED SPECIFIC REQUIREMENTS FOR THE MONOGRAPH Identification (By Infrared spectroscopy) Assay (By Titrimetry) Impurities (By Gravimetry, Titrimetry & Visual Observation) Loss of Drying (By Gravimetry) Methenamine Mandelate Mandelic Acid Residue on Ignition Chloride and Sulfate MANDATORY GENERAL CHAPTERS BELOW <1000> INFORMATIONAL GENERAL CHAPTERS ABOVE <1000> GENERAL NOTICES OF THE PHARMACOPEIA (USP) <731> Loss on Drying <41> Balances <1251> Weighing on an Analytical Balance <197> SPECTROSCOPIC IDENTIFICATION TESTS (k) <854> MID INFRARED SPECTROSCOPY <1854> MID INFRARED SPECTROSCOPY—THEORY AND PRACTICE <1058> ANALYTICAL INSTRUMENT QUALIFICATION <541> TITRIMETRY <31> VOLUMETRIC APPARATUS <630> VISUAL COMPARISON <281> RESIDUE ON IGNITION STANDARDS & REAGENTS USP Reference Standard (RS) Volumetric Solution (VS) Silica Gel Methenamine Mandelate RS Volumetric Solutions 0.05 N silver nitrate in dehydrated alcohol 0.05 N ceric ammonium nitrate VS The General Notices and Requirements section (the General Notices) presents the basic assumptions, definitions, and default conditions for the interpretation and application of the United States Pharmacopeia (USP) and the National Formulary (NF). Requirements stated in these General Notices apply to all articles recognized in the USP and NF (the "compendia") and to all general chapters unless specifically stated otherwise. Methenamine Mandelate