Status: Version etectve from 01/012018, Haemodialysis Solutions General Notices (Solutions for Haemodalyss, Ph. Eur. monograph 0126) Pheur DEFINITION ‘Solutions of electrolytes with a concentration close to the electroltic composition of plasma. Glucose may be included inthe formulation. Because ofthe large volumes used, haemodialysis solutions are usually prepared by luting @ concentrated solution wih water of sultable quali (see ihe monograph fisemodilvss solutions, concentrated. water for diuting (1167), using for example an automatic dosing device. CONCENTRATED SOLUTIONS FOR HAEMODIALYSIS Concentrated haemodialysis solutons are prepared and stored using materials and methods designed to produce solons having as low a degree of ‘mierobal contamination as possible. In certain ercumstances,f may be necessary to use sterile soksons During liuton and use, precautions are taken to void microbial contamination. Diuted solutions are to be used immediately after preparation Concentrated solutions for haemodialysis are supple in — aid, semirgi or teste plaste containers —alass containers, 3 types of concentrated solutions are used 4. Concentrated solutions with otate or lactate ‘Several formulations of concentrated solutions are used. The concentrations of the components inthe solitons are such that, fr dition tote stated volume, the concentrations ofthe components per lire are usually in the folowing ranges (see Table 0128-1): “ihe 028-1 Comat) ‘neg Concentrated solutions with acetate or lactate are diluted before use, 2, Concentrated acid solutions ‘Several formulations of concentrated solutions are used. The concentrations of the components inthe solitons are such that afer dition fo the stated volume and befere neuralsation vith sodium hydrogen carbonate, the concentrations ofthe components pe ire are usualy in the following ranges. (00 Table 0128.2} ‘Sodium hydrogen carbonate must be added immediately before use to a final concentration of nat more than 45 mmol. The concentrated solution of sodium hydrogen carbonate is suppled ina separate container. The concentrated acd solutions and the concentrated sokitions of sodium hydrogen carbonate ae diluted and mixed immediately before use using a suitable device, Aternatvely, sodium hydrogen carbonate in powder form may be sed to prepare the solution. 3, Concentrated solutions without butfor‘mai ‘0 ptm eas ou ‘Several formulations of concentrated solutions without buffer ae used. The concentatons of the components inthe solulons are such that, after luton to the stated volume the concentvations ofthe components per ite are usual inthe folowing ranges (see Table 0128-3): ‘co ana Concentrated solutions without butfer are used together with parenteral administration of suitable hydrogen carbonate sobions IDENTIFICATION According othe stated compeston the sokiton tobe examined gives the folowing entiation reactions (2.9 potassium: reaction () —aloum: reaction (a — sodium reaction —enordes: reaction a) —lacates —earbonates and hydrogen carbonates — acetates: —it tne solution is ree rom glucose, use reacton (b) =f solution contains glucose, use the folowing method: to § mL ofthe soltlon to be examined add 1 ml of hydrochloric acid Rin atest tube fited wth a stopper and a bent tube, heat and collect a few mills of dstllate; cary out reaction (bof acces on the esti; magnesium: fo 0.1 mL of itan velow solution add 10 mL of water F, 2 mL ofthe solution tobe examined and 1 mL of a 42 gil soliton of sodium nydrouide a pink colour is produced —glcose: o 6 mL ofthe solution to be examined add 2 mL of clue sodium hydroxide solution 2 and 0.08 ml of cooper sulfate solution B; the solution s blue and clear; heat to boling; an abundant rea precipitate is formes. TESTS ‘The solution o be examined is clear (2.21). It does nol contain glucose itis colouless (2.22. Method D, Hit contains glucose, iis not more inlensely coloured than reference solution Y, (2.2.2, Method ‘Aluminium (2.4.17) Maximum 0. mgitPrescribed solution Take 20 ml of the solution to be examined, adjust fo pH 6.0 using 01M hydrochloric acid or 0.1 M sodium hydroxide and add 10 mL of acetate butfer solution pM 6.08. Reference soluton M1 ml. of aluminium standard solution (2 om AD R. 10 mL of acetate buler salon pH 6.0 8 and 9 mi. of water [lank solution Mix 10 mL of scstote buffer solution of 6.0.2 and 40 mL of water R, Extractable volume (2.9.17) ‘The volume measured isnot ess than the nominal volume stated onthe abel Microbi TAMG: accoptance enerion 102 OFUIML (2.672). ‘Stertty (2.6.1) ithe label states thatthe concentrated haemodialysis solution's ster, complies wih the test for strity ‘Bactorial endotoxins (2.6.14) Less than 0.25 IUim inthe soliton died for use. Pyrogens (2.6.5) ‘Solutions for wnich a validated ts! for bacterial endoloxins cannot be carried out comply with the Les for nyiogens. Dut the soon fo be examined with water for intections Ro the concentration prescrive for use, Inject 10 mi. ofthe sokiion per kilogram af the rabbis mass, ASSAY Determine the density (2.2.5) ofthe concentrated solution and calculate the cantnt in grams per litre and in milimoles per ire, Sodium 97-5 per cent to 102.5 percent ofthe content of soaium (Na) stated on the label ‘Alomic emission spectrometry (2.2.22, Method ). Test solution Ifnecossary, lute the soliton to be examined with water to a concentration suitable for the instrument tobe used Reference solutions Prepare the reference solutions using sodium stansard solution (200 ppm Na R, Wavelengths 589.0 nm or 589.6 nm (Sodium emits as a double Potassium 95,0 percent o 105.0 percent ofthe content of potassium (K) stated on the label ‘Alomie absorption spectrometry (22.29, Method 0. Test solution Ditte wth water an accurately weighed quantity ofthe solution tobe examined o a concentration sutable fr the instrument to be sed, To 100 mL of ths soluton add 10 mL of a 22 gL solution of sosium chione Reference solutions Prepare the reference solutions using potassium standard solution (100 pom KJ To 100 mL ef each reference solution add 10 mL of 22 gi. solution of soclum chloride R. Source Potassium holow-cathode lamp. Wavelength 788.5 nm ‘Atomization device Ai-acetylene flame. ateium 95.0 per cent to 105.0 percent ofthe content of calcium (Ca) stated onthe label‘Alomic absoraton spectrometry (2.2.23, Method D. Test solution Die 6.0 mi of the Solution Io be examined to 100.0 mL with water 8 To 3.0 mL ofthis Solution add § mL of latnanum chloride solion and lute to 80,0 mL with water Reference solutions Ino 4 identical volumetric asks each containing § mL of lanthanum chloride solution f, introduce respectively 2.5 mi, 5.0 mL, 7.0 mL and 10.0 mi of calcium standerd solution (10 ppm Ca) R and dite to 60.9 mL wth water R. Source Calcium hotlow-cathode lamp. Wavelength 422.7 am, Alomization device Ai-acatylene flame. Magnesium 195.0 per cent to 105.0 percent ofthe content of magnesium (Ma) stated on te label ‘Alomie absorption spectrometry (2.2.29, Method p. Test solution Die §.0 mi of the solution tobe examined 19 100.0 mL with water, To 2.0 ml of this solution add § mL of lanthanum chionae, solution 2 and lute to 60,0 mL wth water Reference solutions. Ino 4 identical volumetric asks each containing § mi of lanthanum chloride solution R, introduce respectively 1.0 mi, 2.0 mL, 3.0mL and 4.0 mL of magnesium standard solution (10 ppm Ma) R and dite to 60.0 mL with water, Source Magnesium hollow-cathode lamp, Wavelensth 286.2 nm Alomisation device Ai-acetylene fame. Total chloride 195.0 per cent to 105.0 percent ofthe content of chloride (Cl stated onthe label Dilute to 50 mL wth water ® an accurately measured volume of the solution fo be examined containing the equivalent of about 60mg of chive. Add '5 mL of dite nite acid R, 25.0 ml of 0.1 M sve nitrate and 2 mL of cibul! phthalate R, Shake, Using 2 mL of ferric ammonium culate solution R2 a8 Indicator, irate with 0.1 M ammonium thiocyanate unt a reddish-yetow colour is obtained. 4 mi of 0.10 siver ntrate is equivalent o 3.545 mg of Cl. Acetate te stated on the hbel 95.0 per cent to 105.0 percent ofthe content of ace Toa volume ofthe solution tobe examined, corresponding to about 0.7 mmol of acetate, add 10.0 mL of 0.1 M hydrachovc acd. Cary out @ potentiometistiration (22.20), using 9.1 M sodium hydride, Read the volume added between the 2 points af infexion, 4 mL of 10 soci hydride fs equivalent to 0.1 mmol of acetate, Lactate 95.0 per cent to 105.0 per cont ofthe content of lactate stated on the label ‘To.a volume ofthe solution tobe examined, corresponding lo about 0.7 mmat of eta, add 10.0 mL of 01M husrachloric acid. Then add 60 mL of 2celoninie &. Cary out a potentiometric ration (22.20), using 0 4M sodium hydroxide. Read the volume added between the 2 points of ilexion. 4 ml of 0.11 socium hysroxise is equivalent to 0.1 mmol of lactate. ‘Sodium hydrogen carbonate 95.0 per cent to 105.0 percent ofthe content of soaium hysrogen carbonate stated on the label irate with 0.1 hydrochloric acid a volume of the solution te be examined corresponding o about 0.1 g of sodium hydrogen carbonate, determining ‘he end-point potentometically (2.220,‘mL of 01M hystochloric acids equivalent to 8.40 mg of NBHCO,, Reducing sugars (expressed as glucose): 95.0 per cent to 105.0 per cent ofthe content of glucose stated on the label ‘Transfer a volume ofthe solution tobe examined containing the equivalent of 26 mg of glucose fo @ 260 mL conical ask with a ground-glass neck and {344 25.0 mL. of cunriaine solution R. Add a few grains of pumice, fia reflux condenser, heat so that doling occurs within 2 min and maintain boing for exactly 10 min, Cool and add 39 of potassium ioe dissolved in 3 ml of water. Careful add, in small amounts, 25 mL of a 25 percent mn solution of sulfuric acid. irate wth 0.1 M sodium thiosulfate using starch solution R, added towards the end ofthe tivation, as indicator. Carry out a blank titration using 25.0 mL of water Calculate the content of reducing sugars, expressed as ghicose (C,H,,0,), using Table 0128-8 ‘eon. "oa a a ‘aac fa = STORAGE ‘Ata temperature not lower than 4 *C. LABELLING The label states: —the formula of the concentrated solution for haemodialysis expressed in grams per Hire and in millmoles per Mire =the nominal volume ofthe soltion in the container —where applicable, tna the concentrated solution s stele =the storage constions; —that the concentrated solution i to be cited immediately before use =the dition to be made; thal the volume taken for use is to be measured accurately =the ionic formula for the ailted solution reagy for use in mitmoles pe tre; —that any unused potion of solution is to be discarded, —where applicable, that sodium hydrogen carbonate isto be added before use, Preur © Crown Copyright 2017 a vw