18,19-Dinorpregn-4-en-20-yn-3-one, 13-ethyl-17-hydroxy-, (17α)-(−)-;
(−)-13-Ethyl-17-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one [797-63-7]
BRIEFING
Levonorgestrel. This proposal is based on the version of the monograph official as of May 1, 2020. On the basis of comments received, the proposal published in PF 41(5) [Sep.–Oct. 2015] has been canceled and is replaced with the following proposal. It is proposed to revise the monograph with the following changes:
-
Revise Identification A to allow flexibility of using either 197A or 197K.
-
Delete the test for Melting Range or Temperature in Identification B and in the Specific Tests section because the remaining tests are sufficient.
-
Add Identification C based on the chromatographic retention time agreement in the proposed Assay.
-
The liquid chromatographic procedure in the Assay was validated using the Purospher STAR RP-18e brand of column with L1 packing. The typical retention time for levonorgestrel is about 13 min.
-
Add the calculation equation to the Limit of Ethynyl Group test.
-
Add the test for Limit of Levonorgestrel 5,7,9-Triene and 3-Methoxy Levonorgestrel 1,3,5-Triene because these impurities are not covered in the proposed Organic Impurities test. The liquid chromatographic procedure was validated using the YMC-Pack ODS-AQ brand of column with L1 packing. The typical retention times for ethinyl estradiol and levonorgestrel are about 9 and 13 min, respectively.
-
Replace the TLC procedure in the test for Organic Impurities with an HPLC procedure. The procedure was validated using the SymmetryShield RP8 brand of column with L7 packing. The typical retention time for levonorgestrel is about 19 min.
-
Add the storage temperature in the Packaging and Storage section based on approved manufacturer's storage conditions.
-
Add USP Ethinyl Estradiol RS, USP Levonorgestrel-5(10)-ene Isomer RS, USP Norethindrone RS, USP Levonorgestrel System Suitability Mixture A RS, and USP Levonorgestrel System Suitability Mixture B RS to the USP Reference Standards section to support the proposed tests for Limit of Levonorgestrel 5,7,9-Triene and 3-Methoxy Levonorgestrel 1,3,5-Triene and Organic Impurities.
Additionally, minor editorial changes have been made to update the monograph to current USP style.
(SM5: M. Chang)
Case ID—SUB-1114