title: Stability of tramadol with three 5-HT3 receptor antagonists in polyolefin bags for patient-controlled delivery systems.
abstract: BACKGROUND
  Mixing 5-hydroxytryptamine-3 (5-HT3) receptor antagonists with patient-controlled analgesia (PCA) solutions of tramadol has been shown to decrease the incidence of nausea and vomiting associated with the use of tramadol PCA for postoperative pain. However, such mixtures are not commercially available, and the stability of the drug combinations has not been duly studied. The study aimed to evaluate the stability of tramadol with three 5-HT3 receptor antagonists in 0.9% sodium chloride injection for PCA administration.
  
  
  METHODS
  Test samples were prepared by adding 1,000 mg tramadol hydrochloride, 8 mg ondansetron hydrochloride, and 6 mg granisetron hydrochloride or 5 mg tropisetron hydrochloride to 100 mL of 0.9% sodium chloride injection in polyolefin bags. The samples were prepared in triplicates, stored at either 25°C or 4°C for 14 days, and assessed using the following compatibility parameters: precipitation, cloudiness, discoloration, and pH. Chemical stability was also determined using a validated high-pressure liquid chromatography method.
  
  
  RESULTS
  All of the mixtures were clear and colorless throughout the initial observation period. No change in the concentration of tramadol hydrochloride occurred with any of the 5-HT3 receptor antagonists during the 14 days. Similarly, little or no loss of the 5-HT3 receptor antagonists occurred over the 14-day period.
  
  
  CONCLUSIONS
  Our results suggest that mixtures of tramadol hydrochloride, ondansetron hydrochloride, granisetron hydrochloride, or tropisetron hydrochloride in 0.9% sodium chloride injection were physically and chemically stable for 14 days when stored in polyolefin bags at both 4°C and 25°C.
authors.affiliation: Department of Pharmacy, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China.
authors.forename: Fu-Chao
authors.initials: FC
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Pharmacy, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China.
authors.forename: Fang-Jun
authors.initials: FJ
authors.lastname: Yuan
authors.affiliation: Department of Pharmacy, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, People's Republic of China.
authors.forename: Lin-Hai
authors.initials: LH
authors.lastname: Wang
mesh_terms: D016503:Drug Delivery Systems; D004355:Drug Stability; D006801:Humans; D011090:Polyenes / Q000737:chemistry*; D044406:Receptors, Serotonin, 5-HT3 / Q000378:metabolism*; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000737:chemistry / Q000494:pharmacology*; D014147:Tramadol / Q000737:chemistry*
chemical_list: D011090:Polyenes; D044406:Receptors, Serotonin, 5-HT3; D058831:Serotonin 5-HT3 Receptor Antagonists; D014147:Tramadol; C035051:PL 732
keywords: granisetron; ondansetron; patient-controlled analgesia; postoperative pain; tramadol; tropisetron