(kar' boe prost troe meth' a meen).
21H36O5· C4H11NO3 489.64
Prosta-5,13-dien-1-oic acid, 9,11,15-trihydroxy-15-methyl-, (5Z,-9,11,13E,15S)-, compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1).
(Z)-7-[(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(E)-(3S)-3-hydroxy-3-methyl-1-octenyl]cyclopentyl]-5-heptenoic acid compound with 2-amino-2-(hydroxymethyl)-1,3-propanediol (1:1).
(15S)-15-Methylprostaglandin F2 tromethamine [58551-69-2].
» Carboprost Tromethamine contains not less than 95.0 percent and not more than 105.0 percent of C25H47NO8, calculated on the dried basis.
[CautionGreat care should be taken to prevent inhaling particles of Carboprost Tromethamine and exposing the skin to it. ]
Packaging and storage Preserve in well-closed containers, and store in a freezer.
USP Reference standards 11
Specific rotation 781S: between +18 and +24.
Test solution: 10 mg per mL, in alcohol.
Loss on drying 731 Dry it in vacuum at a pressure not exceeding 5 mm of mercury at 50 for 16 hours: it loses not more than 1.0% of its weight.
Residue on ignition 281: not more than 0.5%.
Limit of 15R-epimer and 5-trans isomer
Mobile phase, Internal standard preparation, Citrate buffer, and Chromatographic system Proceed as directed in the Assay. To evaluate the system suitability requirements, use the Standard preparation prepared as directed in the Assay.
Test solution Use the Assay preparation.
Procedure Inject a volume (about 25 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the peak areas. Calculate the percentage of the 15R-epimer (as the tromethamine salt) in the portion of Carboprost Tromethamine taken by the formula:
100rA / (rA + rB + rC)in which rA is the area of any peak at a relative retention time of 0.7; rB is the area of any peak at a relative retention time of 1.0; and rC is the area of any peak at a relative retention time of about 1.2. Not more than 2.0% is found. Calculate the percentage of the 5-trans isomer (as the tromethamine salt) in the portion of Carboprost Tromethamine taken by the formula:
100rC /(rA + rB + rC)in which the terms are as defined above. Not more than 3.0% is found.
Mobile phase Prepare a filtered and degassed mixture of methylene chloride, 1,3-butanediol, and water (992:7:0.5). Make adjustments if necessary (see System Suitability under Chromatography 621).
Internal standard preparation Using the Mobile phase, prepare a solution containing about 7 mg of guaifenesin per mL.
Citrate buffer Dissolve 10.5 g of citric acid in about 75 mL of water. Add 5 N sodium hydroxide slowly to adjust to a pH of 4.0, and dilute with water to 100 mL.
Standard preparation Transfer about 5 mg of USP Carboprost Tromethamine RS, accurately weighed, to a stoppered, 50-mL centrifuge tube. Add 20.0 mL of methylene chloride and 2 mL of Citrate buffer. Shake the stoppered tube for about 10 minutes, and centrifuge. Remove and discard the top (aqueous) layer, and transfer a 4.0-mL aliquot of the lower (methylene chloride) layer to a suitable vial. Evaporate with the aid of a stream of nitrogen to dryness. Add 100 µL of a freshly prepared solution of -bromo-2¢-acetonaphthone in acetonitrile (1 in 50). Swirl to wash down the sides of the vial. Add 50 µL of a freshly prepared solution of diisopropylethylamine in acetonitrile (1 in 100), swirl again, and place the vial in a suitable heating device maintained at a temperature of 30 to 35 for not less than 15 minutes. Evaporate the acetonitrile from the vial with the aid of a stream of nitrogen, add 2.0 mL of Internal standard preparation, mix, and pass the resulting solution through a fine-porosity filter. Protect the filtered solution from light prior to injection to prevent degradation of the naphthacyl ester of carboprost.
Assay preparation Proceed as directed for Standard preparation, except to use Carboprost Tromethamine in place of USP Carboprost Tromethamine RS.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm × 30-cm stainless steel column that contains 10-µm packing L3. The flow rate is about 1.8 mL per minute. Chromatograph the Standard preparation, and record the responses as directed for Procedure: the relative retention times for guaifenesin and the 2-naphthacyl ester of carboprost are about 0.6 and 1.0, respectively; the resolution, R, between guaifenesin and the 2-naphthacyl ester of carboprost is not less than 4.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the quantity, in mg, of C25H47NO8 in the portion of Carboprost Tromethamine taken by the formula:
W(RU / RS)in which W is the weight, in mg, of USP Carboprost Tromethamine RS taken to prepare the Standard preparation; and RU and RS are the peak response ratios of the 2-naphthacyl ester of carboprost to the internal standard obtained from the Assay preparation and the Standard preparation, respectively.
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USP35NF30 Page 2498Pharmacopeial Forum: Volume No. 30(1) Page 82