title: Long-Term Stability of Tramadol and Ketamine Solutions for Patient-Controlled Analgesia Delivery.
abstract: BACKGROUND
  Subanesthetic doses of ketamine as an adjuvant to tramadol in patient-controlled analgesia (PCA) for postoperative pain have been shown to improve the quality of analgesia. However, there are no such commercially available drug mixtures, and the stability of the combination has rarely been assessed.
  
  
  METHODS
  Admixtures were assessed for periods of up to 14 days at 4°C and 25°C. Three different mixtures of tramadol and ketamine (tramadol 5.0 mg/mL + ketamine 0.5 mg/mL, tramadol 5.0 mg/mL + ketamine 1.0 mg/mL, and tramadol 5.0 mg/mL + ketamine 2.0 mg/mL) were prepared in polyolefin bags by combining these 2 drugs with 0.9% sodium chloride (normal saline [NS]). The chemical stability of the admixtures was evaluated by a validated high-performance liquid chromatography (HPLC) method and by measurement of pH values. Solution appearance and color were assessed by observing the samples against black and white backgrounds. Solutions were considered stable if they maintained 90% of the initial concentration of each drug.
  
  
  RESULTS
  The percentages of initial concentration of tramadol and ketamine in the various solutions remained above 98% when stored at 4°C or 25°C over the testing period. No changes in color or turbidity were observed in any of the prepared solutions. Throughout this period, pH values remained stable.
  
  
  CONCLUSIONS
  The results indicate that the drug mixtures of tramadol with ketamine in NS for PCA delivery systems were stable for 14 days when stored in polyolefin bags at 4°C or 25°C.
authors: Department of Anesthesiology, enmin Hospital of Wuhan University, Wuhan, Hubei, China (mainland).
authors: Junfeng
authors: J
authors: Gu
authors: Department of Pharmacy, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei, China (mainland).
authors: Wengang
authors: W
authors: Qin
authors: Department of Pharmacy, Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei, China (mainland).
authors: Fuchao
authors: F
authors: Chen
authors: Department of anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China (mainland).
authors: Zhongyuan
authors: Z
authors: Xia
mesh_terms: D016058:Analgesia, Patient-Controlled / Q000379:methods*; D000700:Analgesics / Q000008:administration & dosage / Q000737:chemistry; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004338:Drug Combinations; D004349:Drug Packaging; D004355:Drug Stability; D004356:Drug Storage; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007649:Ketamine / Q000008:administration & dosage* / Q000737:chemistry*; D019999:Pharmaceutical Solutions / Q000008:administration & dosage / Q000737:chemistry; D011090:Polyenes; D013997:Time Factors; D014147:Tramadol / Q000008:administration & dosage* / Q000737:chemistry*
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D004338:Drug Combinations; D019999:Pharmaceutical Solutions; D011090:Polyenes; D014147:Tramadol; D007649:Ketamine; C035051:PL 732