title: Stability of latanoprost in generic formulations using controlled degradation and patient usage simulation studies.
abstract: OBJECTIVE
  To evaluate the stability of latanoprost in generic formulations by using controlled degradation and patient usage simulation studies
  
  
  METHODS
  Standard latanoprost was subjected to controlled degradation studies. Latanoprost content was assessed by using MRM, and generated Degradation Products (DP) were analysed by using the Information Dependent Acquisition (IDA) protocol of positive ESI-LC-MS/MS. Latanoprost content and formation of DP were assessed in generic formulations and were compared with Xalatan(®) in a controlled patient usage simulation studies. The last few drops of latanoprost, present in containers used by patients were also evaluated.
  
  
  RESULTS
  Extreme pH conditions, oxidation, light and heat were found to be the significant factors for high degree of latanoprost degradation. Systematic analysis of 7 selected generics revealed that the latanoprost content varied from 90-330%. Concentration of the latanoprost in Xalatan was found to be 97% of the label claim. Degradation studies showed the formation of 3 novel and 3 already known impurities. Upon simulated patient usage, 2 of the generic formulations showed significant degradation of latanoprost. Generic formulations having thermally sealed gas tight packing showed good stability during patient usage. Overage of latanoprost was observed in generics with other than thermal sealing. Latanoprost bottles used by patients showed concentrations ranging from 20 to 250% of label claim (144% median).
  
  
  CONCLUSIONS
  This study revealed the presence of overage of latanoprost in some generic formulations and formation of degradation products. Packaging with gas tight containers may be one of the important factors for latanoprost stability, along with its storage at low temperature during patient usage.
authors.affiliation: Department of Ocular Pharmacology & Pharmacy, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences , New Delhi , India and.
authors.forename: Thirumurthy
authors.initials: T
authors.lastname: Velpandian
authors.forename: Ankita
authors.initials: A
authors.lastname: Kotnala
authors.forename: Nabanita
authors.initials: N
authors.lastname: Halder
authors.forename: Alok Kumar
authors.initials: AK
authors.lastname: Ravi
authors.forename: Vikneshwari
authors.initials: V
authors.lastname: Archunan
authors.forename: Ramanjit
authors.initials: R
authors.lastname: Sihota
mesh_terms: D000959:Antihypertensive Agents / Q000737:chemistry; D002853:Chromatography, Liquid; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D016568:Drugs, Generic / Q000737:chemistry*; D006801:Humans; D000077338:Latanoprost; D018696:Neuroprotective Agents; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
chemical_list: D000959:Antihypertensive Agents; D016568:Drugs, Generic; D018696:Neuroprotective Agents; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost
keywords: Degradation; generics; glaucoma; latanoprost; stability