EUROPEAN PHARMACOPOEIA 10.0 2.2.5, Relative density Tempertare Potaniam —Potaiim Potaniam —Potaniam —Tolusium — Potawium — Diodium Sodom Calsiom Tic etraralate hydrogen dihydrogen hydrogen dihydrogen Skydropen tetaborate carbonate ydrode, ‘osM "tartate’ crate” phthalste ‘Phosphate Dhawphate|““DO1M”~—“OGISM saturated atcrntedat 005M Tosa Toousat" Son? ° wae are + + Sodiom, Disodium — Dsodtum bearbonate Inydsogen hydrogen ‘ons M phosphate phosphate ors ‘Ooses CHKO,2H,O GHLKO, GHKO, G\HEKO, KH,PO,_KH,PO, Na0,NaCO,r Ca(OH), NaHPO, —NalPO, 1010" NalICO, at son 90014 -00m2 + 00012 “noms 000-000 00M (pit variation per degre Gaon PREPARATION OF REFERENCE BUFFER SOLUTIONS Potassium (etraoxalate 0.05 M. Distolve 12.61 g CALKO, 211,0 in carbon dioxide-free water Rand dilute to 1600.0 mii with the same solvent. Potassium hydrogen tartrate, saturated at 25 °C. Shake an excess of CKO, vigorously with carbon dioxide free water R at 25 °C. Filter or decant, Prepare immediately before use. Potassium dihydrogen citrate 0.05 M. Dissolve 11.41 g of CJH,KO, in carbon dioxide-free water R and dilute to 1000.0 ml. with the same solvent. Prepare immediately before Potassium hydrogen phthalate 0,05 M. Dissolve 10.13 g of CALKO, previously dried for 1 at 110.4 2°C, in carbon oxide free water R and dilute to 1000.0 ml. with the same solvent, Potassium dihydrogen phosphate 0.025 M + Disodium hydrogen phosphate 0.025 M, Dissolve 3.39 g of KH,PO, and 3.53 g of Na,IIPO, both previously dried for 2h at 120 +2 °C, in carbon dioxide free water R and dilute to 1000.0 ral. with the same solvent, Potassium dihydrogen phosphate 0.0087 M + Disodium hydrogen phosphate 0.0303 M. Dissolve 1.18 g of KH,PO, and 4.30 g of Na,FPO, both previously dried for 2 hat 120 + 2°C, in carbon dioxide-free water R and dilute to 1000.0 ma. with the same colvent. Disodium tetraborate 0.01 M. Dissolve 3.80 g of Na,B,0,,10H1,0 in carbon dioxide-free water R and dilute to 1000.0 ml. with the same solvent. Store protected from, atmospheric carbon dioxide, Sodium carbonate 0,025 M + Sodium hydrogen carbonate 0.025 M. Dissolve 2.64 g of Na,CO, and 2.09 g of NaHCO, in carbon dioxide-free water R and dilate to 1000.0 ml. with the same solvent. Store protected from atmospheric carbon dioxide, Calcium hydroxide, saturated at 25 °C. Shake an excess of calcium hydroxide R with carbon dioxide-free water Rand decant at 25 °C. Store protected from atmospheric carbon, dioxide, STORAGE OF BUFFER SOLUTIONS. Store butler solutions in suitable chemically-resistant, airtight containers, such as type I glass bottles or plastic containers suitable for aqueous solutions. a 2.2.4. APPROXIMATE pH OF SOLUTIONS termine the approximate pH using a pH indicator strip R Alternatively, pH indicators such as those described in ‘Table 2.2.4.1 can be used. 01/2016:20204 ‘Table 224-1 React aH Allalne oe ed ims paper R Sghyathane 10 Pherae ston 8 Thyml be solution R Songyallaline >10 Phenolpthalen paper ® Paymol ve sltion R Neutral Metiy ed olaton R Phenol red slut R ‘Acid ‘Met soation R Bromthymol Bue rion RY Sighy aad Met ve solution R Bromocrsl green sulaton R Strong acd <4 Be 2.2.5. RELATIVE DENSITY ‘The relative density ofa substance isthe ratio ofthe mass ofa certain volume of'a substance at temperature f, to the ‘mass of an equal volume of water at temperature f, {Congo red poperR (01/2008:20205 corrected 10.0 ‘Unless otherwise indicated, the relative density 42 is used Relative densityis alto commonly expressed asd, Density Py Alfined asthe mass ofa unit volume ofthe substance at 20°C ‘General Notices (1) apply to all monographs and other texts2.2.6, Refractive index EUROPEAN PHARMAC POEIA 10.0 may also be used, expressed in kilograms per cubic metre or grams per cubic centimetre (1 kgm" r ‘Quantities are related by the following equations where density, 4s expressed in grams per cubic centimetre yy = 0998203 « 132 oF A = 1.00180 % py, Py) = 0999972 x A? or di? = 00008 * py a3! = 0.998230 xd Relative density or density is measured according to the umber of decimals prescribed in the monogeaph using a density bottle (solids or liquids), a hydrostatic balance (olids), a hydrometer (liguids) or a digital density meter With an oscillating transducer (liquids and gases). When the determination is made by weighing, the buoyancy of air is ‘isregarded, which may introduce an error of 1 unit in the 5° decimal place, When using a density meter, the buoyancy of air has no influence Oscillating transducer density meter. The apparatus consists of: = a U-shaped tube, usually of borosilicate glass, which contains the liquid to be examined; = amagneto electrical or piezo-clectrial excitation system. that causes the tube to oscillate as a cantilever oscillator ata characteristic frequency depending on the density of the liquid to be examined; = ameanz of measuring the oscillation period (T), which may. be converted by the apparatus to give a ditect reading of density, or used to calculate density using the constants A and B described below. ‘The resonant frequency (f) is a function of the spring constant (c) and the mass (m) of the system: f= Henee Introduction of 2 constants A = c/ (4m? x V) and B= M/V, leads tothe classical equation forthe oscilating transducer AxT?-B The constant A and Bare determined by operating the ingtroment with the U-tube filled wth 2 dierent samples at known density, for example, degesed water Rand sir Contra measurements are made daly using degased water R. The results displayed forthe control measurement using degassed water R shall not deviate from the reference valve (a= 0.998203 geem 2 = 1.000000) by more than its specified error For example an instrument specified to ‘001 gem’ shall display 09982 + 0.0001 gems” in ander tobe suitable for farther measurement, Otherwise a eadjastmentis necessary. Calibration with certified reference Ihateras is carted out rgularly. Measurements are made tsing the same procedure as for calibration. The liguid to be examined is equilbrated ina thermostat 20 °C before snteodsction int the tbe, i neceesary to avoid the formation tf Bubbles and to reduce the Une required for measurement Factors affecting accuracy include: = temperature uniformity throughout the tube: = non-linearity over a range of density = parasitic resonant effets: = viscosity, whereby solutions with a higher viscosity than the cabrant have a density that is apparently higher than the tae vale ‘The effect of non-linearity and viscosity may be avoided by using calibrants that have density and viscosity elose to those ‘of the liquid to be examined (+ 5 per cent for density, +50 per cent lor viscosity). The density meter may have functions for automatic viscosity correction and for correction of errors avising from temperature changes and non-linearity. ‘Precision is a function of the repeatability and stability of the ‘oscillator frequency, which is dependent on the stability of the volume, mass and spring constant of the cell, Density meters are able to achieve measurements with an certor of the order of 1 x 10"? gem”? to 1 x 10"° gem” anda repeatability of 1 x 10°! gem? to 1 x 10" gem Es 2.2.6. REFRACTIVE INDEX “The refractive index of« medium with reference to air sequal to the ratio ofthe sine ofthe angle of incidence ofa beam of light in arto the sine of the angle of refraction ofthe reracted ‘beam in the given medium, Unless otherwise prescribed, the refractive index is measured 4620. 0.5°C with reference tothe wavelength ofthe D line ‘of sodium (X= 589.3 nim; the symbol i thea n Refractometers normally determine the critical angle In such apparatus the estential par ira prism of known refractive index in contact with the liquid to be examined Calibrate the apparatus using certified reference material, ‘When white ligt is used, the refractometer is provided with a compensating system, The apparatus gives vealings accurate toat least the thd decimal place and is provided witha means ‘of operation atthe temperature prescribed. The thermometer is graduated at intervals of 05°C of less. ey 2.2.7. OPTICAL ROTATION "RINCIPLE, ‘Optical rotation (also known as optical activity) isthe property displayed by chiral substances of rotating the plane fof polarisation of linearly polarised light. ‘Optical rotation is considered to be positive (+) for dextrorotatory substances (ie. thoee that rotate the plane ‘of polarisation in a clockwise dizection when viewed in the direction facing the oncoming light beam) and negative (~) for laevorotatory substances (Le. anticlockwise rotation) "The angle of optical rotation « of a liquid isthe angle of rotation of the plane of polarisation, expressed in degrees (*), x the wavelength of the D-line of sodium (A = 589.3 nm) ‘meatured at 20°C through the liquid when using a path length of 1.00 dm. (01/2008:20206 07/2018:20207 The specific optical rotation [a ofa substance in solution is caleulated from the angle of apical rotation, as defined above, with reference to a path length of 1,00 dim anda concentration substance tobe examined of pal, The specific optical mn ofa substance in solution slays expressed with {eference toa given solvent and concentration ‘As some equipment may not use sodium lamps, the wavelength ‘of measurement is given as 589 nm instead of 589.3 nm, In certain cases specified in the monograph, the angle of optical rotation is measured a other lemperatires, ther wavelengths and/or in cells with a pathlength other than 100 dim 26 ‘See the information section on general monographs (cover pages)