Method Validation for Quantitative Heavy Metals Testing USP Proposed lt 2. Injectable Drug Substance. Authors Tania Russell, Assistant Manager and Nikki Schopp, Team Leader, Analytical Services Department, SGS Life Science Services, Lincolnshire, USAIn 2. US Pharmacopeia USP began proposing changes to the existing USP lt 2. Heavy Metals Tests. These changes are necessary as the current USP lt 2. The United States Penitentiary, Canaan USP Canaan is a highsecurity United States federal prison for male inmates, with a satellite prison camp for minimum. SciELO The Scientific Electronic Library Online SciELO is an electronic library covering a selected collection of Brazilian scientific journals. Clotrimazole Cream USP, 1 contains clotrimazole, a synthetic antifungal agent having the chemical name 1oChloro, diphenylbenzylimidazole the molecular. Learn about Jinteli Norethindrone Acetate and Ethinyl Estradiol Tablets, USP may treat, uses, dosage, side effects, drug interactions, warnings, patient labeling. USP lt 2. 31 is a color based method that is only sensitive enough for certain elements Pb, Hg, Bi, As, Sb, Sn, Cd, As, Cu and Mo. The test is not specific, nor does it provide adequate recovery of the elements being tested. The USP is continuing to modify a proposal for using inductively coupled plasma ICP and ICP mass spectroscopy ICP MS to detect contaminating heavy metals in drug products. The new USP lt 2. Although incorporation of these changes into the USP has been postponed, the current goal is to harmonize USP, European Pharmacopoeia EP and ICH methods. Usp 36 Full' title='Usp 36 Full' />Here is the Full Project on Online Test in Java Language with Full Project Report, Presentation in PowerPoint and Source Code. USPE has an enormous supply of new and used HFO powerplants, HFO generators, diesel generators, natural gas turbines, Cat generators, Cummins generators, and a large. ESTRACE Cream estradiol vaginal cream, USP, 0. WARNING ENDOMETRIAL CANCER, CARDIOVASCULAR DISORDERS, BREAST CANCER and PROBABLE DEMENTIA. Usp 36 Full' title='Usp 36 Full' />The proposed USP methods would test for Class 1 As, Cd, Hg and Pb and Class 2 Cu, Cr, Ir, Mo, Ni, Os, Pd, Pt, Rh, Ru and V elemental impurities. The suggested EP methods would test for class 1. A Pt and Pd, Class 1. B Ir, Rh, Ru, Os, Class 1. C Mo, Ni, Cr, B, Class 2 Cu and Mn and Class 3 Fe and Zn elemental impurities. Lastly, the proposed International Conference on Harmonization ICH methods would test for Class 1 As, Pb, Cd, and Hg, Class 2. USPE sells, ships, and services containerized HFO powerplants, HFO generators, diesel generators, diesel gensets, and natural gas turbines around the world. R and L Slaughter Ltd. England. Our growing range of products are used in industrial, government. A V, Mo, Se and Co, Class 2. B Ag, Au,Tl, Pd, Pt, Ir, Os, Rh and Ru, Class 3 Sb, Ba, Li, Cr, Cu, Sn and Ni and Class 4 B, Fe, Zn, K, Ca, Na, Mn, Mg, W and Al elemental impurities. Validation Parameters. USP, UHM sign MOU via videoconference 014536 pm The University of the South Pacific USP has leveraged the use of Information and Communications. USP testing can either be validated as a limit test or quantitative test. Limit test validation involves performing accuracy and repeatability testing at the limit and specificity. Quantitative validation involves assessing accuracy at 5. Determining sample preparation and analysis on the instrument raises certain challenges that need to be addressed. Sample preparation needs to be complete and the sample must contain relatively low levels of dissolved solids. Instrument methods need to take into consideration possible interferences and strategies for overcoming any interferences encountered. Produkty/ASG_produkty/Pistolety/2_5690_HK_USP_45_Match_links_t4.jpeg' alt='Usp 36 Full' title='Usp 36 Full' />Sample preparation is crucial when validating a quantitative method. Determining a Sample Preparation. The USP proposes neat, direct or indirect testing methods. The direct testing method is used for assessing typical injectable drug products however, multiple sample preparations are occasionally necessary. For the direct method, the sample is prepared in a dilute acid and analyzed directly on the instrument. In contrast, the indirect method involves first a closed vessel microwave digestion step, which is then followed by analysis on the instrument. Nitric acid and hydrochloric acid are the most commonly used acids. When choosing acids for direct or indirect sample preparation, a few considerations are necessary. Using  ICP MS to detect arsenic at low levels in chloride matrices is often difficult because of the 4. Ar. 35. Cl interference in the plasma. Because 4. 0Ar. 35. Cl has the same mass to charge ratio as arsenic, its formation causes a positive interference for the detection of arsenic. During microwave digestion, nitric acid is the best oxidizer for arsenic and thus is most commonly used however, some elements are more compatible with hydrochloric acid than nitric acid. Osmium is difficult to work with due to its high volatility and conversion to osmium tetroxide in the presence of nitric acid, which may result in false readings. Additionally, when testing for mercury, a stabilizer such as gold III chloride Au. Cl. 3 is typically added to maintain mercury as the mercuric ion and to prevent reduction to elemental mercury. Hence, while a single sample preparation method would be ideal, it is generally unlikely that only one will suffice. For the particular injectable drug product discussed here, As, Hg, Ru, Cd, Pb, Cr, Mo, Pd, and V were tested using a direct method with nitric acid osmium was tested using a direct method with hydrochloric acid and Ni, Cu, Ir, Pt and Rh were tested using an indirect microwave digestion. Validation Requirements and Results for a Quantitative Test. Table 1 summarizes the parenteral limits as defined in the proposed USP lt 2. Click on the image to view full sizeThe method validation data for the ICP MS experiments performed in our laboratory demonstrate accuracy Table 2, precision Table 3, ruggedness Table 4, and specificity Table 5. Click on the image to view full sizeClick on the image to view full sizeClick on the image to view full sizeClick on the image to view full sizeLimit of quantitation LOQ, range and linearity are demonstrated by meeting the accuracy requirements. Conclusion. The USP proposed lt 2. ICP and ICP MS instrumentation and methodology expertise, as well as a broad depth of sample preparation knowledge. Instrument set up, the system for sample introduction and plasma discharge are integral aspects of successful method validation. Also important is formulating strategies to overcome sample interferences and achieve acceptable elemental recovery criteria. SGS has the level of expertise necessary to overcome multiple interference types, including high arsenic and osmium recoveries, unstable mercury values and difficult sample preparations, including the use of Hydrofluoric Acid HF in the digestion process, just to name a few. SGS has successfully validated specificity, linearity, accuracy, precision and ruggedness in the methods used for several types of samples, including injectable drug products. SGSs extensive experience with the USP proposed methodology will ultimately ensure a smooth transition for implementation of the new USP, EP and ICH requirements. References. USP General Chapter lt 2. Elemental Impurities Limits, USP 3. NF 3. 1, pp. 1. 51, 6. USP General Chapter lt 2. Elemental Impurities Procedures, USP 3. NF 3. 1, pp. 1. 53, 6. General Notices USPApparatus. A specification for a definite size or type of container or apparatus in a test or assay is given solely as a recommendation. Where volumetric flasks or other exact measuring, weighing, or sorting devices are specified, this or other equipment of at least equivalent accuracy shall be employed. See also Thermometers 2. Volumetric Apparatus 3. Weights and Balances 4. Where low actinic or light resistant containers are specified, clear containers that have been rendered opaque by application of a suitable coating or wrapping may be used. Where an instrument for physical measurement, such as a spectrophotometer, is specified in a test or assay by its distinctive name, another instrument of equivalent or greater sensitivity and accuracy may be used. In order to obtain solutions having concentrations that are adaptable to the working range of the instrument being used, solutions of proportionately higher or lower concentrations may be prepared according to the solvents and proportions thereof that are specified for the procedure. Where a particular brand or source of a material, instrument, or piece of equipment, or the name and address of a manufacturer or distributor, is mentioned ordinarily in a footnote, this identification is furnished solely for informational purposes as a matter of convenience, without implication of approval, endorsement, or certification. Items capable of equal or better performance may be used if these characteristics have been validated. Where the use of a centrifuge is indicated, unless otherwise specified, the directions are predicated upon the use of apparatus having an effective radius of about 2. Unless otherwise specified, for chromatographic tubes and columns the diameter specified refers to internal diameter ID for other types of tubes and tubing the diameter specified refers to outside diameter OD. Steam Bath. Where the use of a steam bath is directed, exposure to actively flowing steam or to another form of regulated heat, corresponding in temperature to that of flowing steam, may be used. Where the use of a water bath is directed without qualification with respect to temperature, a bath of vigorously boiling water is intended. Assay and test procedures are provided for determining compliance with the Pharmacopeial standards of identity, strength, quality, and purity. In performing the assay or test procedures in this Pharmacopeia, it is expected that safe laboratory practices will be followed. This includes the use of precautionary measures, protective equipment, and work practices consistent with the chemicals and procedures used. Prior to undertaking any assay or procedure described in this Pharmacopeia, the individual should be aware of the hazards associated with the chemicals and the procedures and means of protecting against them. This Pharmacopeia is not designed to describe such hazards or protective measures. Every compendial article in commerce shall be so constituted that when examined in accordance with these assay and test procedures, it meets all the requirements in the monograph defining it. However, it is not to be inferred that application of every analytical procedure in the monograph to samples from every production batch is necessarily a prerequisite for ensuring compliance with Pharmacopeial standards before the batch is released for distribution. Data derived from manufacturing process validation studies and from in process controls may provide greater assurance that a batch meets a particular monograph requirement than analytical data derived from an examination of finished units drawn from that batch. On the basis of such assurances, the analytical procedures in the monograph may be omitted by the manufacturer in judging compliance of the batch with the Pharmacopeial standards. Automated procedures employing the same basic chemistry as those assay and test procedures given in the monograph are recognized as being equivalent in their suitability for determining compliance. Conversely, where an automated procedure is given in the monograph, manual procedures employing the same basic chemistry are recognized as being equivalent in their suitability for determining compliance. Compliance may be determined also by the use of alternative methods, chosen for advantages in accuracy, sensitivity, precision, selectivity, or adaptability to automation or computerized data reduction or in other special circumstances. Such alternative or automated procedures or methods shall be validated. However, Pharmacopeial standards and procedures are interrelated therefore, where a difference appears or in the event of dispute, only the result obtained by the procedure given in this Pharmacopeia is conclusive. In the performance of assay or test procedures, not fewer than the specified number of dosage units should be taken for analysis. Proportionately larger or smaller quantities than the specified weights and volumes of assay or test substances and Reference Standards may be taken, provided the measurement is made with at least equivalent accuracy and provided that any subsequent steps, such as dilutions, are adjusted accordingly to yield concentrations equivalent to those specified and are made in such manner as to provide at least equivalent accuracy. To minimize environmental impact or contact with hazardous materials, apparatus and chemicals specified in Pharmacopeial procedures also may be proportionally changed. Where it is directed in an assay or a test that a certain quantity of substance or a counted number of dosage units is to be examined, the specified quantity or number is a minimal figure the singlet determination chosen only for convenience of analytical manipulation it is not intended to restrict the total quantity of substance or number of units that may be subjected to the assay or test or that should be tested in accordance with good manufacturing practices. Where it is directed in the assay of Tablets to weigh and finely powder not fewer than a given number, usually 2. Tablets, it is intended that a counted number of Tablets shall be weighed and reduced to a powder. The portion of the powdered tablets taken for assay is representative of the whole Tablets and is, in turn, weighed accurately. The result of the assay is then related to the amount of active ingredient per Tablet by multiplying this result by the average Tablet weight and dividing by the weight of the portion taken for the assay. Similarly, where it is directed in the assay of Capsules to remove, as completely as possible, the contents of not fewer than a given number, usually 2. Capsules, it is intended that a counted number of Capsules should be carefully opened and the contents quantitatively removed, combined, mixed, and weighed accurately. The portion of mixed Capsules contents taken for the assay is representative of the contents of the Capsules and is, in turn, weighed accurately. The result of the assay is then related to the amount of active ingredient per Capsule by multiplying this result by the average weight of Capsule content and dividing by the weight of the portion taken for the assay. Casio Digital Camera Exilim Software Testing. Where the definition in a monograph states the tolerances as being calculated on the dried or anhydrous or ignited basis, the directions for drying or igniting the sample prior to assaying are generally omitted from the Assay procedure.