WHO Drug Information Vol. 23, No. 1, 2009 - World Health ...

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WHO Drug Information Vol 23, No. 1, 2009Consultation DocumentCalculate the content of oxytocin peptide (C 43H 66N 12O 12S 2) from the declared content ofC 43H 66N 12O 12S 2in oxytocin RS.Additional requirement for Oxytocin for parenteral useBacterial endotoxins. Carry out the test as described under 3.4 Test for bacterialendotoxins; contains not more than 300 IU of endotoxin per mg.ImpuritiesThe following list of known and potential impurities that have been shown to be controlledby the tests of this monograph is given for information [structures and systematicnames to be included].A. Carbimido oxytocinB. AcetyloxytocinC. α-dimerD: β-dimerOXYTOCINUM INJECTIOOXYTOCIN INJECTIONDraft proposal for the International Pharmocopoeia (January 2009).Please address any comments to Quality Assurance and Safety: Medicines,World Health Organization, 1211 Geneva 27, Switzerand. Fax+4122791 4730 or e-mail to rabouhansm@who.intDescription. A clear, colourless liquid.Category. Uterine-stimulating (Oxytocic).Storage. Oxytocin injection should be kept protected from light and, unless otherwiseindicated on the label, stored at a temperature between 2∫C and 8∫C.Labelling. The designation on the container should state the content in IU per ml andthe oxytocin peptide (C 43H 66N 12O 12S 2) content in mg per ml.Additional information. Strength in the current WHO Model list of essential medicines:10 IU per ml in 1-ml ampoule.Oxytocin injection is normally intended for intravenous or intramuscular administration.While it is expected that stocks of Oxytocin injection will be stored at 2 ˚C to 8 ˚C in,for example, a hospital pharmacy, small amounts may be held for short periods (30days) without refrigeration, for example, on a labour ward trolley or by a midwife. Anysupplies so held and not used within this period should be discarded.43
Consultation DocumentWHO Drug Information Vol 23, No. 1, 2009[Note from the Secretariat: Comment on this aspect of the revised draft togetherwith any supporting stability data would be much appreciated.]REQUIREMENTSOxytocin injection complies with the monograph for “Parenteral preparations”.Definition. Oxytocin injection is a sterile solution of Oxytocin in a suitable diluent.Oxytocin injection contains not less than 90.0% and not more than 110.0% of theamount of the peptide C 43H 66N 12O 12S 2stated on the label.Identity testsEither test A or test B may be applied.A. Carry out the test as described under 1.14.1 Thin-layer chromatography, usingsilica gel R5 as the coating substance and a mixture of 70 volumes of dichloromethaneR, 30 volumes of methanol R, 6 volumes of purified water and 1 volume of glacialacetic acid R as the mobile phase. Apply separately to the plate 20 µl of each of thefollowing two solutions. For solution (A) evaporate 10.0 ml of oxytocin injection todryness at 30 ˚C under reduced pressure (not exceeding 0.6 kPa or 5 mm of mercury)and dissolve the residue in 1.0 ml of methanol R. Prepare solution (B) in methanol Rcontaining 165.0 µg/ml of oxytocin RS. After removing the plate from the chromatographicchamber, allow it to dry exhaustively in a current of cool air. Expose the plateto iodine vapour and examine in daylight.The principal spot obtained with solution A corresponds in position, appearance, andintensity with that obtained with solution B.B. Examine the chromatograms obtained in the Assay. The principal peak in thechromatogram obtained with the test solution is similar in retention time to the principalpeak in the chromatogram obtained with the reference solution.pH value. (2.3) pH of the injection, 2.5–5.0.Assay. Determine by 1.14.4 High performance liquid chromatography, using a stainlesssteel column (25 cm x 4.6 mm) packed with particles of silica gel the surface ofwhich has been modified with chemically bonded octadecylsilyl groups (5 µm).(Eurosper 100–5 is suitable.)Use the following conditions for gradient elution:Mobile phase A: 15 volumes of acetonitrile R, 15 volumes of phosphate buffer and 70volumes of water R. (Eurosper 100–5 is suitable.)Mobile phase B: 70 volumes of acetonitrile R, 15 volumes of phosphate buffer and 15volumes of water R.Prepare the phosphate buffer by dissolving 31.2 g of sodium dihydrogen phosphatedihydrate R in 1000 ml of water R.44
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