2. Academic Validation
  3. Analysis of verteporfin liposomal formulations for phospholipids and phospholipid degradation products by liquid chromatography-mass spectrometry (LC-MS)

Analysis of verteporfin liposomal formulations for phospholipids and phospholipid degradation products by liquid chromatography-mass spectrometry (LC-MS)

  • J Pharm Biomed Anal. 2022 Jan 20:208:114473. doi: 10.1016/j.jpba.2021.114473.
Siyam M Ansar 1,  Wenlei Jiang 2,  Thilak Mudalige 3
Affiliations

Affiliations

  • 1 Arkansas Laboratory, Office of Regulatory Science, Office of Regulatory Affairs, US Food and Drug Administration, Jefferson, AR 72079, USA.
  • 2 Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993, USA. Electronic address: Wenlei.Jiang@fda.hhs.gov.
  • 3 Arkansas Laboratory, Office of Regulatory Science, Office of Regulatory Affairs, US Food and Drug Administration, Jefferson, AR 72079, USA. Electronic address: Thilak.mudalige@fda.hhs.gov.
PMID: 34814079 DOI: 10.1016/j.jpba.2021.114473
Abstract

Lipid composition and lipid degradation are critical to the stability of liposomal formulations which can impact the safety and efficacy of the drug. Herein we developed and validated an ultrahigh performance liquid chromatography coupled with quadrupole time of flight mass spectrometry (UPLC-QTOF-MS) method for determining phospholipid composition and phospholipid degradation products in a verteporfin liposomal formulation (Visudyne). The high mass accuracy (<5 ppm) of the QTOF method coupled with database searching (SimLipid) and comparison with known standards accurately identified and quantified the phospholipid compositions and lipid degradation products. The analysis of Visudyne indicated that more than 50% (w/w) of the total Phospholipids are composed of phosphatidylcholine (PC) 14:0-14:0 and major phosphatidylglycerol (PG) species found are PG 16:0-18:2, PG 16:0-18:1, PG 18:0-18:2, and PG 18:0-18:1. The LC-MS method developed is capable of separating structural isomers such as PG 18:1-18:1 versus PG 18:0-18:2 and the separation of PG stereoisomers, such as PG 18:1-18:1 cis and PG 18:1-18:1 trans. The major lipid degradation products in Visudyne includes lysophosphatidylcholine and a few saturated and unsaturated lysophosphatidylglycerols, and free fatty acids (FFA). Each degradation product is less than 1% of the total Phospholipids (w/w). In addition, the lipid profiles of naturally sourced egg PG from six different vendors were compared with the PG composition in Visudyne. Differences in lipid composition in egg PGs from different vendors were observed and the PG composition in Visudyne is matched with the lipid profile of the some of the egg PGs from different vendors. Drug developers can utilize this method to assess raw Materials and lipid-based drug product quality and regulatory scientists can monitor the quality of the drug available in the market using this validated method.

Keywords

LC-MS; Lipid composition; Lipid degredation products; Liposome; Visudyne.

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