Microbiological and Physicochemical Stability of Fentanyl, Oxycodone, Hydromorphone, Ketorolac, Ramosetron, and Ondansetron for Intravenous Patient-controlled Analgesia: An In Vitro Study.

BACKGROUND: Postoperative patient-controlled analgesia provides pain relief, encourages early mobilization, and results in a shortened hospital stay. Patient-controlled analgesia involves the mixing of different types of drugs. When using patient-controlled analgesia, it is important to confirm the microbiological and physicochemical stability of each drug in a mixture to guarantee that the drug is delivered to the patient in an unaltered form. OBJECTIVES: To confirm the microbiological and physicochemical stability of various drug mixtures for intravenous patient-controlled analgesia. STUDY DESIGN: An in vitro protocol to examine the microbiological and physicochemical stability of the most commonly used postoperative intravenous patient-controlled analgesia mixtures at our institution. SETTING: In vitro laboratory study. METHODS: Each mixture contained a total of 4 drugs: fentanyl 400 µg, ketorolac 30 mg, either hydromorphone 4 mg or oxycodone 10 mg, and either ramosetron 0.3 mg or ondansetron 10 mg. Each mixture was placed in a portable patient-controlled analgesia system containing 0.9% saline and stored at a constant temperature of 24°C for 96 hours. Physical properties (color, transparency, and sedimentation) were observed with the naked eye and optical microscopy. Sterility testing was performed to assess microbiological contamination in the drug mixture during the 96-hour study period. The pH of each mixture was evaluated for up to 96 hours after mixing. The concentration of each drug was evaluated by high-performance liquid chromatography every 24 hours until 96 hours after mixing. RESULTS: All mixtures appeared visibly transparent, and no sediments were visible under the microscope. Bacterial or fungal growth was not observed in any of the samples after 14 days of incubation. The pH variations in all mixtures were maintained within 0.25 over the 96-hour study period. The concentration of drugs, except ketorolac, ranged from 90-110% of the initial concentration up to 96 hours after mixing. In the mixtures with a pH of 4.21-4.39, the concentration of ketorolac significantly decreased at 24 hours and 48 hours. LIMITATIONS: Confirmation of the stability of drugs in vitro does not automatically ensure that the pharmacokinetics and pharmacodynamics of the drugs are not altered in vivo. CONCLUSION: With the exception of ketorolac, the drugs used in the intravenous patient-controlled analgesia drug mixtures in this study were physicochemically stable up to 96 hours after mixing. The concentration of ketorolac decreased in more acidic mixtures.

On-chip immunoassay of a cardiac biomarker in serum using a polyester-toner microchip.

An on-chip immunoassay to detect C-reactive protein (CRP) was performed using a polyester-toner (PT) microchip. CRP is a highly conserved plasma protein responding to inflammation and is used for clinical purposes to diagnose an inflammatory state. For rapid analysis and specific interactions in immunoassays, extensive studies using microfluidic chips have been carried out. Recently, a simple technique to fabricate a disposable PT microchip by a direct printing process was developed and several applications were introduced. One major drawback of the PT microchip, however, is the poor separation performance due to the quality of the microfluidic structures. This problem for a PT microchip can be overcome using a cleavable tag immunoassay, which requires minimal separation performance. After analytes are conjugated onto antibodies which are immobilized on the surface of microbeads placed on the PT microchip, a second group of fluorescently tagged antibodies are added and complexed with the analytes. The tag is then cleaved and the solution containing the cleaved tag is analyzed by electrophoresis. The time needed for the complete analysis to be carried out on a PT microchip was less than 35 min. The dynamic range of the CRP in 10-fold diluted serum was 0.3-100 mg/L and the limit of detection was 0.3 mg/L, which demonstrated the possibility of a quantitative analysis of CRP in serum in clinical trials.