BRIEFING

 Sodium N-(Carbonyl-Methoxypolyethylene Glycol 2000)-1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine. Because there is no existing USP monograph for this excipient, a new monograph based on validated methods of analysis is proposed. The monograph title, Sodium N-(Carbonyl-Methoxypolyethylene Glycol 2000)-1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine, was approved by the USP Nomenclature and Label Expert Committee. The name is consistent with the GSRS database and FDA Inactive Ingredient Database (IID). The following are highlights of the proposed tests in this new monograph:

1. The fatty acid composition gas chromatography (GC) method for Identity by Fatty Acid Composition as well as the thin-layer chromatography method (Identification of Phospholipids by Thin-Layer Chromatography) are added as Identification tests. The validated GC method is based on analyses using the Agilent CP-Wax 52 CB brand of column with G16 phase. The typical retention times for methyl palmitate, methyl stearate, methyl oleate, and methyl arachidonate are 26.5, 30.6, 30.7, and 33.9 min, respectively.

2. The Assay is based on a validated HPLC method performed using the Ultrasphere Octyl C8 brand of column with L7 packing. The typical retention times for sodium N-(carbonyl-methoxypolyethylene glycol 2000)-1,2-palmitostearoyl-sn-glycero-3-phosphoethanolamine, sodium N-(carbonyl-methoxypolyethylene glycol 2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine, and sodium N-(carbonyl-methoxypolyethylene glycol 2000)-1,2-stearoicosanoyl-sn-glycero-3-phosphoethanolamine are 20.7, 22.9, and 23.2 min, respectively.

3. The Limit of Polyethylene Glycol Monomethyl Ether 2000 and Sodium N-(Carbonyl-Methoxypolyethylene Glycol 2000)-1-Stearoyl-sn-Glycero-3-Phosphoethanolamine test under the Impurities section is based on the same validated HPLC method as the Assay. The typical retention times for polyethylene glycol monomethyl ether 2000 and sodium N-(carbonyl-methoxypolyethylene glycol 2000)-1-stearoyl-sn-glycero-3-phosphoethanolamine are 10.0 and 14.2 min, respectively.

4. The other Impurities tests, Limit of Free Fatty Acid as Stearic Acid and Limit of Free 1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine, were analyzed using thin-layer chromatography with densitometer detection to quantify these impurities.

5. The Limit of Ethanol test is based on a validated GC headspace procedure with the Agilent DB-1 brand of column with G1 phase. The typical retention time for ethanol is 1.66 min.

6. The test for Average Molecular Mass Determination is based on a validated HPLC method performed using the Zorbax Eclipse, XDB-C18 brand of column with L1 packing. The identification of the single polyethylene glycol monomethyl ether species of the sample is done by comparison of the retention time of the most intensive peak with those of the standard chromatogram.

 (CE: A. Chang)

 Case ID—SUB-583