Pentoxifylline
(pen'' tox if' i lin).
Click to View Image
C13H18N4O3 278.31
1H-Purine-2,6-dione, 3,7-dihydro-3,7-dimethyl-1-(5-oxohexyl)-.
1-(5-Oxohexyl)theobromine [6493-05-6].
» Pentoxifylline contains not less than 98.0 percent and not more than 102.0 percent of C13H18N4O3.
Packaging and storage— Preserve in well-closed containers.
USP Reference standards 11—
USP Pentoxifylline RS Click to View Structure
Completeness of solution 641— Solution in carbon dioxide-free water (1 in 50) meets the requirements.
Identification—
B: Ultraviolet Absorption 197U—
Solution: 0.01 mg per mL.
Medium: water.
Absorptivities at 274 nm, calculated on the dried basis, do not differ by more than 3.0%.
Melting range, Class I 741: between 104 and 107.
Acidity— Dissolve about 1 g in 50 mL of carbon dioxide-free water, and add 1 drop of bromothymol blue TS: not more than 0.2 mL of 0.01 N sodium hydroxide is required in order to produce a color change.
Loss on drying 731— Dry it in vacuum at 60 for 3 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.1%.
Chloride 221— A 2.0-g portion shows no more chloride than corresponds to 0.31 mL of 0.020 N hydrochloric acid (0.011%).
Sulfate 221— A 1.0-g portion shows no more sulfate than corresponds to 0.20 mL of 0.020 N sulfuric acid (0.02%).
Chromatographic purity—
Perchloric acid solution and Mobile phase— Prepare as directed in the Assay.
System suitability solution— Dissolve accurately weighed quantities of caffeine and USP Pentoxifylline RS in Mobile phase to obtain a solution containing about 0.0007 mg per mL and 0.35 mg per mL, respectively.
Standard solution— Dissolve an accurately weighed quantity of USP Pentoxifylline RS in Mobile phase to obtain a solution having a known concentration of about 0.0007 mg per mL.
Test solution— Dissolve an accurately weighed quantity of Pentoxifylline in Mobile phase to obtain a solution having a concentration of about 0.35 mg per mL.
Chromatographic system (see Chromatography 621)— Proceed as directed in the Assay. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between caffeine and pentoxifylline is not less than 10.0. Chromatograph the Standard solution, and record the peak responses for pentoxifylline as directed for Procedure: the relative standard deviation for replicate injections is not more than 5.0%.
Procedure— Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, and allow the chromatogram to run five times longer than the retention time for the pentoxifylline. Measure the areas of all the peaks in the Test solution, except that for pentoxifylline. Calculate the percentage of each impurity in the portion of Pentoxifylline taken by the formula:
286C(ri / rS)
in which C is the concentration, in mg per mL, of USP Pentoxifylline RS in the Standard solution; ri is the peak area response for each impurity obtained from the Test solution; and rS is the peak area response for pentoxifylline obtained from the Standard solution: not more than 0.2% of any individual impurity is found, and not more than 0.5% of total impurities is found.
Assay—
Perchloric acid solution— Dissolve 1.0 g of perchloric acid in 1000 mL of water, and mix.
Mobile phase— Prepare a filtered and degassed mixture of Perchloric acid solution, acetonitrile, tetrahydrofuran, and methanol (80:15:2.5:2). Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution— Dissolve suitable quantities of caffeine and USP Pentoxifylline RS in Mobile phase to obtain a solution containing 0.024 mg per mL and 0.048 mg per mL, respectively.
Standard preparation— Dissolve an accurately weighed quantity of USP Pentoxifylline RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.05 mg per mL.
Assay preparation— Transfer about 25 mg of Pentoxifylline, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix. Pipet 5.0 mL of the solution so obtained to a 25-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 273-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 0.7 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the resolution, R, between caffeine and pentoxifylline is not less than 10.0. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: 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 responses for the major pentoxifylline peaks. Calculate the quantity, in mg, of C13H18N4O3 in the portion of Pentoxifylline taken by the formula:
500C(rU / rS)
in which C is the concentration, in mg per mL, of USP Pentoxifylline RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison
1-301-816-8349		 (SM22010) Monographs - Small Molecules 2
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
USP35–NF30 Page 4265