Compound impurities and methods of detecting same
View Patent ↗The present disclosure relates to compositions comprising impurities (e.g., carbamate and/or hydrolysis products) in a lomitapide sample and methods of detecting such impurities.
1. A lomitapide product having the following structure:
2. A lomitapide composition comprising: lomitapide or a pharmaceutically acceptable salt thereof the lomitapide product of claim 1 ; and
a pharmaceutically acceptable excipient.
3. A tablet comprising the lomitapide composition of claim 2 .
4. The composition of claim 2 , wherein the lomitapide product is present in an amount of less than about 0.5 weight percent.
5. The composition of claim 2 , wherein the lomitapide product is present in an amount of less than about 0.1 weight percent after storage at 25° C. for 12 months.
6. A method for analyzing a lomitapide composition sample for the presence or amount of an impurity comprising:
providing a lomitapide composition sample;
using a spectral or toxicology analysis to determine the presence of a compound having the structure:
making a determination about the lomitapide composition sample based on a comparison of the compound and a reference standard for lomitapide or a pharmaceutically acceptable salt thereof; and
determining the presence or amount of the compound thereby to analyze the lomitapide composition sample.
7. The method of claim 6 , wherein the determination about the lomitapide composition sample is based on a comparison of a structural signal associated with of the compound and a reference standard for lomitapide or a pharmaceutically acceptable salt thereof.
8. The method of claim 7 , wherein a level of the structural signature is calculated as the area under the curve or as the percent relative amount of each fraction present in the lomitapide composition sample.
9. The method of claim 7 , wherein the structural signature is determined using high performance liquid chromatography (HPLC).
10. The method of claim 7 , wherein the structural signature is determined using nuclear magnetic resonance (NMR) spectroscopy.
11. The method of claim 7 , wherein the structural signature is determined using matrix-assisted laser desorption/ionization mass spectroscopy (MALDI-MS).
12. The method of claim 7 , wherein the structural signature is determined using one or more of a fluorometric assay, an enzyme-linked immunosorbent assay (ELISA), a chromatogenic assay, and a colorimetric assay.
13. The method of claim 7 , wherein the presence of the structural signature associated with the compound is determined to analyze the lomitapide composition sample.
14. The method of claim 6 , wherein the determination about the lomitapide composition sample is based on a comparison of the molecular weight associated with of the compound and a reference standard for lomitapide or a pharmaceutically acceptable salt thereof.
15. The method of claim 14 , wherein the molecular weight associated with the compound is determined to analyze the lomitapide composition sample.
16. A method for determining an amount of an impurity in a composition sample comprising lomitapide or a pharmaceutically acceptable salt thereof, the method comprising:
determining an amount of a compound having the structure:
in the sample; and
correlating the amount the compound in the sample with the amount of lomitapide in the sample.