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. KEY WORDS: Patient-controlled analgesia, multimodal analgesia, stability, fentanyl, oxycodone, hydromorphone, ketorolac, ondansetron, ramosetron

Intravenous patient-controlled analgesia: in vitro stability profiles of mixtures containing fentanyl, hydromorphone, oxycodone, nefopam, ondansetron, and ramosetron

Background and objectives Patient-controlled analgesia often involves combinations of multiple drugs. This study aimed to determine the stability of drug mixtures commonly used for intravenous patient-controlled analgesia. Materials and methods We examined four of the most commonly used drug combinations in intravenous patient-controlled analgesia at our institution. Mixtures contained fentanyl (400 μg), either oxycodone (10 mg) or hydromorphone (4 mg), nefopam (20 mg), and either ondansetron (10 mg) or ramosetron (0.3 mg). Each drug mixture was diluted in 0.9% saline and stored in a portable patient-controlled analgesia system at room temperature (24 °C) for 96 h. Physical attributes including color, turbidity, and precipitation were assessed using digital imaging and optical microscopy. Sterility testing was conducted to assess for microbiological contamination. The pH of each mixture was monitored for up to 96 h after mixing. The concentration of each drug in the mixture was also evaluated using high-performance liquid chromatography. Results All mixtures remained colorless and transparent with no visible sediment for 96 h. After 14 days of culture, none of the samples showed bacterial or fungal growth. The pH for all mixtures was maintained between 4.17 and 5.19, and the mean pH change in any mixture was less than 0.4 over the study period. The concentration of each drug remained between 90 and 110% of the initial value for 96 h after mixing. Conclusion Four drug mixtures commonly used for intravenous patient-controlled analgesia are physiochemically stable and remain sterile for 96 h after mixing.

Predicting the Severity of Adverse Drug Reactions

<p>Polypharmacy, co-prescribing multiple medication, is implausibly common and infrequently ends up in drug interactions that may have adverse facet effects. Currently, to help doctors in prescribing treatments, clinical call systems fireplace alerts once drug mixtures area unit prescribed that have glorious reactions. Those alerts area unit supported drug interaction severity stored in databases like Lexi-Interact. However, Lexi-Interact severity, that is predicated on clinical trials and literature reviews, doesn't embrace all drug interactions tho' there are several prescribed drug mixtures that haven’t been lined by literature. This paper is enforced by coaching a model that has comparatively high accuracy and recall with glorious Lexi-Interact severity values, the goal would be to check it on drug interactions with glorious severity. Specifically, a drug combine would have a foreseen severity so a panel of clinical pharmacists, people acquainted with clinical outcomes of drug interactions, would rate the validity of that foreseen severity. We intend to realize such reactive medication and report them to the doctors.</p>

Quantifying synergy in the bioassay-guided fractionation of natural product extracts

Mixtures of drugs often have greater therapeutic value than any of their constituent drugs alone, and such combination therapies are widely used to treat diseases such as cancer, malaria, and viral infections. However, developing useful drug mixtures is challenging due to complex interactions between drugs. Natural substances can be fruitful sources of useful drug mixtures because secondary metabolites produced by living organisms do not often act in isolation in vivo. In order to facilitate the study of interactions within natural substances, a new analytical method to quantify interactions using data generated in the process of bioassay-guided fractionation is presented here: the extract fractional inhibitory concentration index (EFICI). The EFICI method uses the framework of Loewe additivity to calculate fractional inhibitory concentration values by which interactions can be determined for any combination of fractions that make up a parent extract. The EFICI method was applied to data on the bioassay-guided fractionation of Lechea mucronata and Schinus terebinthifolia for growth inhibition of the pathogenic bacterium Acinetobacter baumannii. The L. mucronata extract contained synergistic interactions (EFICI = 0.4181) and the S. terebinthifolia extract was non-interactive overall (EFICI = 0.9129). Quantifying interactions in the bioassay-guided fractionation of natural substances does not require additional experiments and can be useful to guide the experimental process and to support the development of standardized extracts as botanical drugs.

Stability and Compatibility of Drug Mixtures from Intrathecal Pump Using High Performance Liquid Chromatography

Although management of intractable pain using long-term intrathecal analgesic administration by implantable infusion systems has become acceptable clinical practice, this method presents unique challenges regarding the stability of the pharmaceutical agent(s) delivered. The stability and compatibility of a single drug such as hydromorphone or bupivacaine, as well as mixtures of morphine-clonidine, have previously been reported, but only using implantable infusion systems and syringes under simulated clinical use conditions, not from implanted intrathecal pumps. The objective of this study was to assess the compatibility and stability of drug mixtures from intrathecal pumps placed in patients. For this case-series, 5 patients with intrathecal pumps who presented to the pain clinic for refill were randomly selected. An aliquot of sample extracted from the pump and an aliquot of new medicine used for pump refill were collected. High performance liquid chromatography (HPLC) was used to compare the 2 samples. Drug samples used were as follows: (A) hydromorphone only, (B) morphine and bupivacaine, (C) hydromorphone and ziconotide, (D) ziconotide and baclofen; and (E) hydromorphone, ziconotide, and baclofen. Samples B and E appeared to be stable when placed in situ in the SynchroMed II intrathecal pump based on the HPLC analysis. However, samples A, C, and D appeared to have undergone some degradation and/or byproduct formation as noted in the graphical display on HPLC. While sample A was a single-drug combination, the sample was in the pump for over 3 months; likewise, sample E was a 3-drug combination, however it was in the pump for only 30 days. Based on these results, it appears as though (a) when the length of time the drug stays in the intrathecal pump increases, or (b) when a combination of drugs is used in the intrathecal pump (as opposed to a single drug), some drug degradation and/or byproduct formation happens as seen on HPLC. This is the first reported study assessing the compatibility and stability of drug mixtures from intrathecal pumps. While the above reported HPLC data reveals quantitative differences, further qualitative analysis is required for confirmation and possible identification of possible degradation and/or byproducts. Key words: Degradation, high performance liquid chromatography, intrathecal pump

Enzyme-based paper test for detection of lactose in illicit drugs

A three-enzyme system incorporated into a paper analytical device can semi-quantitatively detect lactose at concentrations as low as 5% in illicit drug mixtures.