scholarly journals Stability and Compatibility of Antibiotics in Peritoneal Dialysis Solutions Applied to Automated Peritoneal Dialysis in the Pediatric Population

2016 ◽  
Vol 36 (6) ◽  
pp. 676-679 ◽  
Author(s):  
Guillaume Deslandes ◽  
Matthieu Grégoire ◽  
Régis Bouquié ◽  
Aude Le Marec ◽  
Sophie Allard ◽  
...  

ObjectivesAssess the stability of several antibiotics in peritoneal dialysis (PD) solutions under common conditions of use in pediatrics, particularly in automated PD.MethodsAmoxicillin, cefazolin, cefepime, ceftazidime, imipenem, cotrimoxazole, tobramycin, vancomycin, and the association of ceftazidime + vancomycin and ceftazidime + tobramycin, were tested in 3 different PD solutions: bicarbonate/lactate solution with 2 glucose concentrations (Physioneal 1.36 and 3.86%; Baxter Healthcare Corporation, Deerfield, IL, USA) and an icodextrin-containing solution (Extraneal; Baxter Healthcare Corporation, Deerfield, IL, USA). Concentrations were those recommended in guidelines for the treatment of peritonitis in pediatrics. Physioneal bags were incubated at 37°C for 24 hours, whereas Extraneal bags were stored 12 hours at room temperature (22 ± 2°C) and then 12 hours at 37°C. Drug concentrations were determined using high performance liquid chromatography (HPLC). Each measure was taken in triplicate. Stability of antibiotics was defined as less than 10% degradation of the drug over time.ResultsCefazolin, cotrimoxazole, tobramycin, and vancomycin were stable under studied conditions. Ceftazidime was stable 24 hours in icodextrin, 12 hours in Physioneal 1.36% and 6 hours in Physioneal 3.86%. The association of tobramycin or vancomycin did not influence the stability of ceftazidime. Cefepime and amoxicillin were stable 6 h, 4 h, and 8 h in Physioneal 1.36%, 3.86% and Extraneal, respectively. The stability of imipenem was very low: 2 h in Physioneal and 6 h in Extraneal. Moreover, an increasingly yellow coloration was observed with the use of imipenem, whereas no color change or precipitation occurred in other bags.ConclusionCefazolin, tobramycin, cotrimoxazole, and vancomycin are stable in PD solutions up to 24 hours and can be administered in the PD bag for the treatment of peritonitis, even in automated PD under studied conditions. However, amoxicillin, cefepime, ceftazidime, and imipenem must be used with caution due to their lack of stability.

2010 ◽  
Vol 23 (6) ◽  
pp. 570-574 ◽  
Author(s):  
Brandon R. Shank ◽  
Clyde M. Ofner

The stability of pergolide mesylate in an oral aqueous liquid was studied. Stability and solubility data were used to determine the degradation characteristics of the drug in this formulation. Samples were stored in the dark at 35°C, 45°C, and 60°C. At 1, 2, 4, 8, 12, and 16 weeks, samples were removed and stored in a −80°C freezer for high performance liquid chromatography (HPLC) assay at a later date. The initial drug concentration of 0.30 mg/mL was determined by assay after storage at −80°C. A solubility of 6.9 mg/mL was found for pergolide mesylate in the oral liquid at room temperature with a relative standard deviation (RSD) of 4.0%. The degradation process is considered first-order at 25°C and 35°C. At higher temperatures (45°C and 60°C), a color change and curvature at the latter time points in degradation profiles are ascribed to the presence of methylcellulose. The activation energy calculated for degradation of pergolide mesylate in the oral liquid was 21.3 kcal/mol. The time to reach 90% potency (t90) values were calculated to be 43 days and 3 days, respectively, for storage at 25°C and 35°C. Drug concentrations up to ~6 mg/mL can be maintained as a solution at room temperature with this formulation.


2004 ◽  
Vol 24 (6) ◽  
pp. 590-595 ◽  
Author(s):  
Markus Voges ◽  
Dirk Faict ◽  
Guy Lechien ◽  
Michel Taminne

Objective To evaluate the stability of gentamicin, tobramycin, netilmycin, vancomycin, cefazolin, unfractionated heparin, and low molecular weight heparin when added to four different peritoneal dialysis (PD) solutions [Extraneal (Baxter Healthcare, Castlebar, Ireland); Physioneal, Nutrineal, and Dianeal (Baxter Healthcare, Grosotto, Italy)] in new, non-PVC Clear-Flex containers. Measurements Gentamicin, tobramycin, netilmycin, vancomycin, cefazolin, unfractionated heparin, and low molecular weight heparin were injected into separate bags of PD solution. Samples were withdrawn at predefined sampling times and the concentration of each drug was analyzed using high-performance liquid chromatography (for gentamicin, tobramycin, vancomycin, and cefazolin), or bioassay (for netilmycin, gentamicin, and tobramycin in Nutrineal), or coagulation methods (heparins). Results Netilmycin, vancomycin, cefazolin, and heparin in Physioneal, Nutrineal, Extraneal, and Dianeal were stable for at least 24 hours at 25°C and for an additional 4 hours at 37°C. Gentamicin in Nutrineal, Extraneal, and Dianeal was stable for at least 24 hours at 25°C and for an additional 4 hours at 37°C; gentamicin in Physioneal was stable for less than 24 hours at 25°C. Tobramycin in Nutrineal and Extraneal was stable for at least 24 hours at 25°C and for an additional 4 hours at 37°C; tobramycin in Physioneal and Dianeal was stable for less than 24 hours at 25°C.


1994 ◽  
Vol 28 (5) ◽  
pp. 572-576 ◽  
Author(s):  
Leigh M. Vaughan ◽  
Cathy Y. Poon

OBJECTIVE: To examine the stability of ceftazidime, vancomycin, and heparin, alone and in combination, in dialysis solution over six days at three temperatures. DESIGN: Nine 250-mL Dianeal PD-2 dextrose 1.5% bags were prepared with ceftazidime, vancomycin, and heparin alone and in combination at set concentrations of 100 μg/mL, 50 μg/mL, and 1 unit/mL, respectively. Three bags of each mixture were stored at 4, 25, and 37°C. Duplicate samples for analysis were removed from each bag at the following time points: premix, 0, 12, 24, 48, 72, 96, 120, and 144 hours. MAIN OURCOME MEASURES: Each sample was examined visually for signs of cloudiness and precipitation. Each sample was analyzed by stability-indicating HPLC assay for ceftazidime and vancomycin, with stability defined as less than 10 percent degradation of drug overtime. RESULTS: No color change or precipitation was observed in any bag. Vancomycin with or without heparin was stable for 5–6 days at 4, 25, and 37°C. Ceftazidime with and without heparin was stable for 6 days at 4°C, 4 days at 25°C, and less than 12 hours at 37 °C. Vancomycin plus ceftazidime with and without heparin was stable for 6 days at 4 °C and 25°C, and 4–5 days at 37 °C, Ceftazidime plus vancomycin with or without heparin was stable for 6 days at 4°C, 2–3 days at 25°C, and 12 hours at 37 °C. CONCLUSIONS: Bulk preparations of ceftazidime and vancomycin, alone and in combination and with or without heparin in Dianeal PD dextrose 1.5% solution, are sufficiently stable for use up to 6 days under refrigeration or 48 hours at room temperature.


2009 ◽  
Vol 29 (1) ◽  
pp. 52-57 ◽  
Author(s):  
Katie E. Pallotta ◽  
Rowland J. Elwell ◽  
Adwoa O. Nornoo ◽  
Harold J. Manley

Purpose The data describing the compatibility of tobramycin and ceftazidime in icodextrin-based peritoneal dialysis (PD) solution is limited. The objective of this study was to assess the chemical stability of tobramycin and ceftazidime in icodextrin PD solution in polyvinyl chloride containers. Methods Commercially available 2-L bags of icodextrin 7.5% PD solution were used for each sample. Nine tobramycin study samples were prepared by adding 80 mg tobramycin HCl to each bag. Nine ceftazidime samples were prepared by adding 1000 mg ceftazidime to each bag. Three bags of tobramycin–icodextrin solution were stored under each of the following conditions: refrigeration (4°C), room temperature (25°C), and body temperature (37°C). Three bags of ceftazidime–icodextrin solution were also stored at each of the respective temperatures. Samples were withdrawn from each bag immediately after preparation and at predetermined intervals (1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 336 hours after preparation). Solutions were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. All samples were immediately frozen (–80°C) after collection and stored prior to assay. Total concentrations of tobramycin and ceftazidime in dialysate fluid were determined by high-performance liquid chromatography. The last time point when tobramycin or ceftazidime concentration was >90% from baseline was used to denote stability. Results All solutions were clear in appearance and no color change or precipitation was observed during the study. For tobramycin, under refrigeration, a mean of 94.6% ± 2.3% of the initial concentration remained at 336 hours (14 days); at room temperature, 90.5% ± 4.3% remained at 168 hours (7 days); at body temperature, 90.0% ± 8.1% remained at 24 hours. For ceftazidime, under refrigeration, a mean of 98.0% ± 0.3% of the initial concentration remained at 168 hours (7 days); at room temperature, 91.6% ± 2.0% remained at 48 hours; at body temperature, 93.9% ± 1.1% remained at 8 hours. Stability was not assessed beyond these respective time points. Conclusion Premixed tobramycin–icodextrin PD solution remains stable for 336 hours (14 days) when refrigerated (4°C) and for 168 hours (7 days) at room temperature (25°C). Ceftazidime–icodextrin PD solution is stable for 168 hours and 48 hours, respectively, when stored at 4°C and 25°C. It is recommended that the bags be kept refrigerated whenever possible. Tobramycin–icodextrin solution stored at body temperature was stable up to 24 hours, and ceftazidime–icodextrin solutions up to 8 hours, permitting the practice of pre-warming solutions prior to administration.


2021 ◽  
Vol 26 (4) ◽  
pp. 395-404
Author(s):  
Ankit Rochani ◽  
Vinh Nguyen ◽  
Robin Becker ◽  
Walter Kraft ◽  
Gagan Kaushal

OBJECTIVE In the hospital settings, buprenorphine is used for the treatment of patients with neonatal abstinence syndrome. It is extemporaneously compounded and stored in oral plastic syringes. However, limited information exists about the stability of buprenorphine and its compounded formulations when stored under specific conditions. Hence, we developed a stability-indicating high-performance liquid chromatography–mass spectrometry (LC-MS) method to analyze the stability of buprenorphine over time. METHODS A stability-indicating LC-MS method was developed to map the potential degradation peaks of buprenorphine when exposed to acidic, basic, and oxidative conditions. This method was used to study the stability of compounded buprenorphine oral syringes stored under refrigeration (2°C–8°C) and room temperature (25°C ± 2°C with 60% relative humidity). Syringes from each storage condition were assessed for stability using pH meter and stability-indicating LC-MS assay for 30 days. RESULTS Buprenorphine gets completely degraded in the presence of acid at the end of 1 hour of exposure. Various degradation peaks were identified using LC-MS assay for buprenorphine under acidic, basic, and peroxide conditions. Stability study of oral buprenorphine syringes showed no precipitation, cloudiness, or color change during this study at all storage conditions. The LC-MS assay revealed that buprenorphine oral syringes retained greater than 90% of the initial concentrations for 30 days. CONCLUSIONS Highly sensitive stability-indicating LC-MS method was developed for studying the stability of extemporaneously compounded buprenorphine oral syringes. This study demonstrates that buprenorphine extemporaneous formulation prepared according to the manufacturers' recommendations is stable under refrigerated or room temperature conditions for 30 days in oral plastic syringes.


2019 ◽  
Vol 55 (3) ◽  
pp. 188-192
Author(s):  
M. L. Colsoul ◽  
A. Breuer ◽  
N. Goderniaux ◽  
J. D. Hecq ◽  
L. Soumoy ◽  
...  

Background and Objective: Infusion containing lorazepam is used by geriatric department to limit anxiety disorders in the elderly. Currently, these infusions are prepared according to demand by the nursing staff, but the preparation in advance in a centralized service could improve quality of preparation and time management. The aim of this study was to investigate the long-term stability of this infusion in polypropylene syringes stored at 5 ± 3°C. Then, results obtained were compared with stability data of lorazepam in syringes stored at room temperature, glass bottles at 5 ± 3°C, and glass bottles at room temperature. Method: Eight syringes and 6 bottles of infusion were prepared by diluting 1 mL lorazepam 4 mg in 23 mL of NaCl 0.9% under aseptic conditions. Five syringes and 3 bottles were stored at 5 ± 3°C and 3 syringes and 3 bottles were stored at room temperature for 30 days. During the storage period, particle appearance or color change were periodically checked by visual and microscope inspection. Turbidity was assessed by measurements of optical density (OD) at 3 wavelengths (350 nm, 410 nm, 550 nm). The stability of pH was also evaluated. The lorazepam concentrations were measured at each time point by high-performance liquid chromatography with ultraviolet detector at 220 nm. Results: Solutions were physically unstable in syringes at 5 ± 3°C after 4 days: crystals and a drop of OD at 350 nm were observed. However, pH was stable. After 2 days, solutions were considered as chemically unstable because a loss of lorazepam concentration higher than 10% was noticed: the lower 1-sided confidence limit at 95% was below 90% of the initial concentration. To assess temperature and polypropylene influence, results were compared with those obtained for syringes at room temperature and bottles at 5 ± 3°C and room temperature. Precipitation, drop of OD at 350 nm, and chemical instability were observed in all conditions. Conclusion: Solutions of lorazepam were unstable after 2 days in syringes at 5 ± 3°C. Preparation in advance appears, therefore, not possible for the clinical use. Storage conditions (temperature and form) do not improve the stability.


2017 ◽  
Vol 37 (1) ◽  
pp. 51-55 ◽  
Author(s):  
Martin Wiesholzer ◽  
Alexandra Winter ◽  
Manuel Kussmann ◽  
Markus Zeitlinger ◽  
Petra Pichler ◽  
...  

BackgroundIntraperitoneal administration of antimicrobial agents is recommended for the treatment of peritoneal dialysis (PD)-related peritonitis. For home-based antimicrobial therapy it is common to supply patients with PD fluid bags with admixed antibiotic. Thus, the compatibility of meropenem with different PD fluids (PDFs), namely Extraneal, Physioneal 1.36% and Physioneal 2.27% (all Baxter Healthcare Corp., Deerfield, IL, USA), was investigated under varying storage conditions.MethodsMeropenem (Venus Pharma, Werne, Germany) was stored at 6°C and 25°C over 14 days and at 37°C over 24 hours. Drug concentration over time was determined using high performance liquid chromatography, drug activity by a diffusion disk method, diluent stability by visual inspection and drug adsorption was calculated. Blank PD fluids and deionized water were used as comparator solutions.ResultsCompared to water, the stability of meropenem was minimally lower in Extraneal but markedly reduced in both Physioneal solutions. No significant drug adsorption was detected for any PDF investigated.ConclusionsMeropenem is stable and compatible with Extraneal and might be stored for up to a week at refrigeration temperature (6°C). A loss of ∼20% of meropenem after 2 days at room temperature should be considered. Mixed Physioneal appears not suitable for storage at any temperature after meropenem has been admixed. A considerable drug degradation due to the warming up to body temperature through heating plates should further be taken into account in clinical practice.


2014 ◽  
Vol 34 (2) ◽  
pp. 212-218 ◽  
Author(s):  
Rahul P. Patel ◽  
Madhur D. Shastri ◽  
Mohammad Bakkari ◽  
Troy Wanandy ◽  
Matthew D. Jose

IntroductionThe objective of this study was to investigate the stability of ceftazidime and cephazolin in a 7.5% icodextrin or pH neutral peritoneal dialysis (PD) solution.MethodsCeftazidime and cephazolin were injected into either a 7.5% icodextrin or pH neutral PD bag to obtain the concentration of 125 mg/L of each antibiotic. A total of nine 7.5% icodextrin or pH neutral PD bags containing ceftazidime and cephazolin were prepared and stored at 1 of 3 different temperatures: 4°C in a domestic refrigerator; 25°C at room temperature; or 37°C (body temperature) in an incubator. An aliquot was withdrawn immediately before (0 hour) or after 12, 24, 48, 96, 120, 144, 168 and 336 hours of storage. Each sample was analyzed in duplicate for the concentration of ceftazidime and cephazolin using a stability-indicating high-performance liquid chromatography technique. Ceftazidime and cephazolin were considered stable if they retained more than 90% of their initial concentration. Samples were also assessed for pH, colour changes and evidence of precipitation immediately after preparation and on each day of analysis.ResultsCeftazidime and cephazolin in both types of PD solution retained more than 90% of their initial concentration for 168 and 336 hours respectively when stored at 4°C. Both of the antibiotics lost more than 10% of the initial concentration after 24 hours of storage at 25 or 37°C. There was no evidence of precipitation at any time under the tested storage conditions. Change in the pH and color was observed at 25 and 37°C, but not at 4°C.ConclusionPremixed ceftazidime and cephazolin in a 7.5% icodextrin or pH neutral PD solution is stable for at least 168 hours when refrigerated. This allows the preparation of PD bags in advance, avoiding the necessity for daily preparation. Both the antibiotics are stable for at least 24 hours at 25 and 37°C, permitting storage at room temperature and pre-warming of PD bags to body temperature prior to its administration.


2018 ◽  
Vol 38 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Surendra Kandel ◽  
Syed Tabish R. Zaidi ◽  
S. Troy Wanandy ◽  
Long C. Ming ◽  
Ronald L. Castelino ◽  
...  

Background Intraperitoneal (IP) administration of ceftazidime is recommended for the treatment of peritoneal dialysis-associated peritonitis (PDAP) from Pseudomonas. Patients with PDAP may also need IP heparin to overcome problems with drainage of turbid peritoneal dialysis (PD) fluids and blockage of catheters with fibrin. Physico-chemical stability of ceftazidime and heparin, and biological stability of heparin in many types of PD solutions is unknown. Therefore, we investigated the stability of ceftazidime and heparin in 4 types of PD solutions. Methods A total of 12 PD bags (3 for each type of solution) containing ceftazidime and heparin were prepared and stored at 4°C for 120 hours, and then at 25°C for 6 hours, and finally at 37°C for 12 hours. An aliquot was withdrawn after predefined time points and analyzed for the concentration of ceftazidime and heparin using high-performance liquid-chromatography (HPLC). Samples were assessed for pH, color changes, particle content, and anticoagulant activity of heparin. Results Ceftazidime and heparin retained more than 91% of their initial concentration when stored at 4°C for 120 hours followed by storage at 25°C for 6 hours and then at 37°C for 12 hours. Heparin retained more than 95% of its initial activity throughout the study period. Particle formation was not detected at any time under the storage conditions. The pH and color remained essentially unchanged throughout the study. Conclusions Ceftazidime-heparin admixture retains its stability over long periods of storage at different temperatures, allowing its potential use for PDAP treatment in outpatient and remote settings.


2003 ◽  
Vol 23 (1) ◽  
pp. 58-62 ◽  
Author(s):  
David P. Dooley ◽  
J. Robert Tyler ◽  
William G. Wortham ◽  
Linda S. Harrison ◽  
William F. Starnes ◽  
...  

← Objective To evaluate the stability of the antimicrobial chemical and bioactivity of gentamicin, vancomycin, and gentamicin and vancomycin in combination, and the stability of the bioactivity of ceftazidime, admixed in standard peritoneal dialysis solutions and then maintained over a 14-day period at room temperature or under refrigeration. ← Setting Peritoneal dialysis center and microbiology laboratory at a military, teaching medical center. ← Measurements Standard peritoneal dialysate bags admixed with gentamicin, vancomycin, gentamicin and vancomycin in combination, or ceftazidime were stored at either 4°C or 20°C for 14 days. Sequential aliquots were withdrawn and assayed for antibiotic activity by bioassay and, except for ceftazidime, immunoassay for chemical activity. The bioassay was performed using a standardized Kirby–Bauer disc method. Significance was determined by ANOVA and, where the effect size was significant at the p < 0.05 level, the application of the paired t-test or the Wilcoxon signed rank test to the difference in activity between the first and last samples. ← Results Antibiotic concentration by immunoassay did not significantly deteriorate over 14 days for vancomycin or gentamicin when either room temperature or refrigerated samples were studied. By bioassay, gentamicin and ceftazidime, but not vancomycin, lost moderate but significant activity over 14 days when refrigerated bags were assayed (except for an insignificant decrement in gentamicin in the combined vancomycin and gentamicin bags). Bags stored at room temperature, in general, lost significant bioactivity over 14 days, but to levels where clinical efficacy would still be expected. The vancomycin bioassay performed on the combination bags demonstrated a remarkably enhanced bioactivity, presumably reflecting synergy with gentamicin. ← Conclusion These data indicate that the study antibiotics admixed with peritoneal dialysis fluids retain stable chemical activity, whether refrigerated or kept at room temperature, for at least 14 days. A moderate decrement in bioactivity occurred for study antibiotics when stored either refrigerated or at room temperature over 14 days, although clinically significant levels were maintained. The clinical significance of a possible synergy between vancomycin and gentamicin is yet to be determined.


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