Analytical and clinical evaluation of four commercial SARS-CoV-2 serological immunoassays in hospitalized patients and ambulatory individuals.

BACKGROUND: This study aimed to compare four anti-SARS-CoV-2 immunoassays in populations presenting different clinical severity levels. METHODS: Three populations were included: "severe-to-critical" ICU-hospitalized patients (n = 18), "mild-to-moderate" hospitalized patients (n = 16) and non-hospitalized symptomatic patients (n = 24). Four commercial immunoassays were analyzed and validated: anti-IgG ARCHITECT® (Abbott), anti-Total antibodies (Ab) VITROS® (Ortho Clinical Diagnostics), anti-IgG NovaLisa® (NovaTec Immundiagnostica) and Healgen® IgM and IgG (Zhejiang Orient Gene Biotech). Sensitivities were evaluated according to days post-symptoms onset (pso). Specificities were evaluated on SARS-CoV-2-negative control sera collected before January 2020. RESULTS: A majority of severe-to-critically ill patients showed detectable Ab already at day 14 and sensitivities reached 100 % after 22 days pso. For patients with "mild-to-moderate" illness, sensitivities increased by at least 5-fold from day 0 to day 14 pso. Non-hospitalized symptomatic individuals already seroconverted at day 14 days pso with 100 % sensitivities for Total Ab VITROS®. Specificities were evaluated at 97 % for ARCHITECT® and NovaLisa®, 98 % for VITROS® and at 94 % for Healgen® combined IgM and IgG. Five "severe-to-critically" ill patients presented high positive Ab levels for at least 16 weeks pso. CONCLUSION: The Ab levels and the evaluated sensitivities, representing the true positive rate, increased overtime and were related to the COVID-19 severity. Automated Total Ab immunoassay showed better sensitivities and specificity for immunological surveillance and vaccine evaluation.

Long-Term Stability of Lorazepam in Sodium Chloride 0.9% Stored at Different Temperatures in Different Containers.

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.

Physical stability of highly concentrated injectable drugs solutions used in intensive care units.

BACKGROUND: The intensive care department of the institution use drug solutions within higher concentration to avoid fluid overload. The purpose of the study is to prove the physical stability of different injectable drugs within high concentration (amiodarone 25mg/mL, isosorbide 0.60mg/mL, lorazepam 0.16mg/mL, noradrenalin 0.120 and 0.240mg/mL, salbutamol 0.06mg/mL and sodium valproate 12mg/mL) to ensure the patients safety. METHODS: Five of 30 or 50mL polypropylene syringes were prepared for each solution under aseptic conditions and stored at room temperature. Immediately after the preparation (hour 0) and after 1, 4, 8, 24 and 48hours, 2mL of each solution were withdrawn from each syringe and placed in glass tubes to proceed to the stability test. All specimens were visually inspected in front of a black and of a white background and aliquots of each solution were centrifuged to proceed to microscopic inspection with a ten-fold magnification. The pH of each solution was measured with glass electrode pH-meter (Inolab level 1, WTW Weilhem, Germany with biotrode electrode, Hamilton, Bonaduz, Switzerland) and spectrophotometric measurements (Genesys 10 series, New-York, USA) were performed at three wavelengths (350, 410 and 550nm) to avoid the apparition of turbidity. RESULTS: For all the drugs included in the study, there was no significant change in pH, no color change, no turbidity or opacity and no precipitation observed in the solutions during the storage at room temperature for 48hours. No microaggregates were detected by microscope neither revealed by a change of absorbance. CONCLUSION: Within these limits, the preparations of amiodarone in 5% glucose polypropylene syringes and isosorbide, lorazepam, noradrenalin, salbutamol, valproate in 0.9% sodium chloride polypropylene syringes are physically stable at room temperature for 48hours. These results allow us to consider a study of chemical stability by high-performance liquid chromatography (HPLC).

Does an interaction exist between ketamine hydrochloride and Becton Dickinson syringes?

INTRODUCTION: An international alert from Becton Dickinson (BD) has noted the possibility of interaction between several molecules and some syringes. The Centralized IntraVenous Additives Service of the institution was using 3 mL BD syringes to store ketamine HCl. This study evaluated the interaction between ketamine and these syringes. METHOD: A batch of BD syringes produced in Europe and left in quarantine from the day of the international alert has been tested at 22, 29, 36, 43 and 50 days of storage at room temperature. At each time, the pH of the solutions was measured. The solutions were inspected visually and by microscope, and spectrophotometric measurements were performed. The concentrations were measured by a validated ultra-high-performance liquid chromatography-diode array detector. RESULTS: Neither physical change nor pH modification was observed during the study. According to a lower limit of the 95% unilateral CI on the mean >90% of the theoretical concentration, the solutions remain stable for at least 50 days. CONCLUSION: In our study conditions, ketamine can be stored for at least 50 days without risk of sorption with syringes.

Long-term stability of dexamethasone and alizapride or ondansetron in sodium chloride 0.9% polyolefin bag at 5±3°C.

INTRODUCTION: The aim of the study was to investigate the long-term stability of dexamethasone 10mg associated with alizapride 100mg or ondansetron 8mg in 100mL of 0.9% sodium chloride solution stored at 5±3°C. METHOD: Solutions of 0.9% sodium chloride 100mL in polyolefin bags (n=5) containing approximately dexamethasone (DEX) 10mg associated with alizapride (ALI) 100mg or ondansetron (OND) 8mg were prepared under aseptic conditions and stored about 30 days at 5±3°C. ALI, DEX and OND concentrations were measured by high-performance liquid chromatography (HPLC). Optic density measurement at different wavelengths, pH measurement and optic microscope observations were performed periodically during the storage. A forced degradation test with HCL 5M and NaOH 5M before and after heating at 100°C was also performed. Solutions were considered stable if the 95% one-sided lower confidence limit of the concentration remains superior to 90% of the initial concentration or 95% of the initial concentration when any signs of physical instability exist as recently recommend. RESULTS: The calibration was linear over the following range from 20 to 1.25mg/100mL for DEX, from 200 to 12.5mg/100mL for ALI and from 20 to 1.25mg/100mL for OND with a calculated correlation coefficient (r2) of 0.998, 0.999 and 0.999, respectively. The inter- and intra-assay precision was below 10% for both mixtures. All formulations were physically stable during the storage. The lower confidence limit of the concentration for these solutions remains superior to 90% of the initial concentration at this date as recommended by the Food and Drug Administration (FDA) until 30 days. CONCLUSION: The HPLC method is specific and reproducible and can easily be adopted for monitoring the quality control in the production of DEX-ALI and DEX-OND bags. Solutions of DEX-ALI and DEX-OND were physically and chemically stable for 30 days in polyolefin bags stored at 5±3°C and could therefore be prepared in advance.

Long-term stability of ketamine hydrochloride 50mg/ml injection in 3ml syringes.

INTRODUCTION: Ketamine hydrochloride (Ketalar(®)) injection is often used as a general anesthetic agent. It is particularly suited to short-term interventions. It can also be used as an inducer of anesthesia before the administration of other anesthetic agents. The aim of this study was to evaluate the stability of ketamine hydrochloride in 3ml polypropylene syringes after storage for up to 180days at room temperature. METHOD: Syringes containing ketamine hydrochloride (50mg/ml) were prepared and stored at room temperature (25°C) for 180days. The concentrations were measured by validated ultra-performance liquid chromatography-diode array detection at 0, 7, 14, 28, 60, 84, 112, 140 and 180days. A degradation test was performed to evaluate the specificity of the analysis. At each time point, the pH, color and visible particles of each solution were also assessed. RESULTS: Degradation tests proved no interfering peaks with ketamine. All solutions were physically stable during the storage. The lower confidence limit of the concentration for these solutions remains superior to 90% of the initial concentration at this date as recommended by the Food and Drug Administration (FDA) until 180days (100%±2%). CONCLUSION: Solutions of ketamine (50mg/ml) were chemically stable for 180days in polypropylene syringes with storage at room temperature and could be prepared in advance by a centralized intravenous admixture service.

[The long-term chemical stability of injectable drugs reconstituted in Hospital Pharmacy]. / Stabilité chimique à long terme de médications injectables reconstituées en Pharmacie Hospitaliére.

BACKGROUND: Other injectable preparations than parenteral nutrition admixture and injectable cytotoxic drugs could be prepared by Centralised IntraVenous Admixture Service (CIVAS) if the Long-term stability of the drugs is known. However, this information is not always available. PURPOSE: To develop a program of chemical drug stability analysis in collaboration between Hospital Pharmacy, Medical Laboratory and Scientific Support Unit to determine the long-term stability of largely used injectable anti-infectious and non-anti-infectious drugs. MATERIAL AND METHODS: After a setup of the High Performance Liquid Chromatography (HPLCI method, 28 drugs were reconstituted in laminar air flow hood, 17 of them stored directly at 5 +/- 3 degrees C and 19 stored in the freezer at -20 degrees C, thawed by microwave following a standardised procedure and stored at 5 +/- 3 degrees C before use. Concentration stability was evaluated by regression analysis. RESULTS: For each drug, long-term stability has varied from 11 days to 180 days. The freeze-thaw treatment by microwave may enhance the stability (from 30 to 120 days) and allow batch-scale production of intravenous drugs, less expensive in term of manpower and sterile device than a drug reconstitution at the ward. The results were published by 55 posters in international congress and by 36 publications in national and international pharmaceutical journals. CONCLUSIONS: Our findings contribute to enhance the scale of drugs that may be take on by a CIVAS.

Microwave freeze-thaw technique of injectable drugs. A review from 1980 to 2014.

OBJECTIVE: Microwave freeze-thaw treatment (MFTT) of injectable drugs can support the development of centralized intravenous admixtures services (CIVAS). The aim of the review is to collect information and results about this method. METHODS: A systematic review of the scientific literature about injectable drug stability studies was performed. The data are presented in a table and describe name of the drug, producer, final concentration, temperature and time of freezing storage, type of microwave oven, thawing power, method of dosage and results after treatment or final long-term storage at 5±3 °C. RESULTS: From 1980 to 2014, 59 drugs were studied by MFTT and the results were presented in 49 publications. Forty papers were presented by 8 teams (2 to 18 by team). The temperatures of freezing storage vary from -70 °C to -10 °C, the time storage from 4 hours to 12 months, the thaw from low to full power. Dosages are mainly made by high performance liquid chromatography. Most of the 59 drugs are stable during and after treatment. Only 3 teams have tested the long-term stability after MFTT, the first for ganciclovir after 7 days, the second for ceftizoxime after 30 days and the third for 19 drugs after 11 to 70 days. CONCLUSIONS: This review can help CIVAS to take in charge the productions of ready-to-use injectable drugs.

Long-term stability of acyclovir in 0.9% NaCl infusion polyolefin bags at 5±3°C after freeze-thaw treatment: a generic product versus the brand name.

INTRODUCTION: The aim of the study was to investigate the long-term stability of acyclovir 5 mg/mL (a generic product versus the brand name) in NaCl 0.9% after storage at 5±3°C and to evaluate the influence of initial freezing and microwave thawing on this stability. METHODS: Five bags of Acyclovir® Hospira 5 mg/mL (A) and five bags of Zovirax® GSK 5 mg/mL (B) were prepared under aseptic conditions and stored 3 months at -20°C, then thawed and stored 30 days at 4°C. Five bags of Acyclovir® 5 mg/mL (C) and five bags of Zovirax® 5 mg/mL (D) were also prepared under aseptic conditions and stored 30 days at 5±3°C. Optic density measurement at different wavelengths, pH measurement and optic microscope observations were performed periodically during the storage. A forced degradation test with HCl 12 M and NaOH 5 M before and after heating at 100°C was also performed. The concentrations were measured by HPLC-PDA. RESULTS: The only one forced degradation test that yielded chromatograms with degradation products peak was the test with the acid solution heated at 100°C without interference with the native product. No significant change in pH values or optic densities were seen during the study for both products. No crystals were seen with the optic microscope during the study. Acyclovir® and Zovirax® solutions were stable for at least 21 days according to the FDA recommendations. Moreover, there was no statistical difference between regression lines of those two products and two storage conditions. CONCLUSION: Under the conditions of this study, Acyclovir® 5 mg/mL in 100 mL of NaCl 0.9% infusion remains stable at least for 21 days at 5±3°C with or without freezing at -20°C during the three previous months. There is no statistical difference between the brand name and a generic product. Acyclovir may be prepared in advanced by a centralized intravenous additive service, frozen in polyolefin bags and microwave thawed before storage under refrigeration until 21 days.

Long-term stability of morphine hydrochloride in 0.9% NaCl infusion polyolefin bags after freeze-thaw treatment and in polypropylene syringes at 5 degrees C + 3 degrees C.

The aim of this study was to investigate the long-term stability of morphine hydrochloride in 0.9% NaCI infusion polyolefin bags and polypropylene syringes after storage at 5 degrees C + 3 degrees C and to evaluate the influence of initial freezing and microwave thawing on this stability. Ten polyolefin bags and five polypropylene syringes containing 100 mL of 1 mg/mL of morphine hydrochloride solution in 0.9% NaCI were prepared under aseptic conditions. Five polyolefin bags were frozen at -20 degrees C for 90 days before storage. Immediately after the preparation and after thawing, 2 mL of each bag were withdrawn for the initial concentration measurements. All polyolefin bags and polypropylene syringes were then refrigerated at 5 degrees C + 3 degrees C for 58 days during which the morphine concentrations were measured periodically by high-performance liquid chromatography using a reversed-phase column, naloxone as internal standard, a mobile phase consisting of 5% acetonitrile and 95% of KH2PO4 buffer (pH 3.50), and detection with diode array detector at 254 nm. Visual and microscopic observations and spectrophotometric and pH measurements were also performed. Solutions were considered stable if the concentration remained superior to 90% of the initial concentration. The degradation products peaks were not quantitatively significant and were resolved from the native drug. Polyolefin bag and polypropylene syringe solutions were stable when stored at 5 degrees C + 3 degrees C during these 58 days. No color change or precipitation in the solutions was observed. The physical stability was confirmed by visual, microscopic, and spectrophotometric inspection. There was no significant change in pH during storage. Freezing and microwave thawing didn't influence the infusion stability. Morphine hydrochloride infusions may be prepared in advance by centralized intravenous additive service, frozen in polyolefin bags, and microwave thawed before storage under refrigeration until 58 days either in polyolefin bags or polypropylene syringes. Such treatment could improve safety and management.

Pyroglutamic acid-induced metabolic acidosis: a case report.

High anion gap metabolic acidosis due to pyroglutamic acid (5-oxoproline) is a rare complication of acetaminophen treatment (which depletes glutathione stores) and is often associated with clinically moderate to severe encephalopathy. Acquired 5-oxoprolinase deficiency (penicillins) or the presence of other risk factors of glutathione depletion such as malnutrition or sepsis seems to be necessary for symptoms development. We report the case of a 55-year-old women who developed a symptomatic overproduction of 5-oxoproline during flucloxacillin treatment for severe sepsis while receiving acetaminophen for fever control. Hemodialysis accelerated the clearance of the accumulated organic acid, and was followed by a sustained clinical improvement.

Microwave freeze-thaw treatment of dose-banded cytotoxics injectable drugs: a review of the literature from 1980 to 2011.

INTRODUCTION: Microwave freeze-thaw treatment (MFTT) of injectable drugs can support the development of centralized intravenous admixtures services (CIVAS). The aim of this review is to collect information about the stability of cytotoxic and hazardous drugs after this treatment. METHODS: The scientific literature about drug stability studies was reviewed. The data describe the name of the drug, the manufacturer, the final concentration, the temperature and time of freezing storage, type of microwave oven, the thawing power, the measurement, the method and the results after treatment and final long-term storage at 5±3°C. RESULTS: From 1980 to 2011, nine drugs (cyclophosphamide, cytarabine, daunorubicine, doxorubicine, epirubicine, fluorouracile, ganciclovir, methotrexate sodium, mitomycine C) were studied after MFTT and the results were presented in 10 publications. The storage freezing temperature ranged from -15°C to -30°C, the time storage from 14 to 364 days, the thaw from moderate to full power. High performance liquid chromatography is mainly used to measure drug concentrations. All drugs are stable during and after the treatment. However, mitomycine needs to be stored at -30°C. The long-term stability after MFTT was evaluated only for the ganciclovir after 7 days, and for fluorouracile after 28 days. The concentration of the seven drugs was measured after one to 11 freezing-thawing cycles with a loss below 5%. CONCLUSIONS: This review can help the hospital pharmacist to take in charge the productions of nine dose-banded ready-to-use injectable cytotoxic and hazardous drugs. Freezing enhances their long-term stability without altering their chemical stability. Validated microwave thawing reduces the time of defrosting of these drugs at the studied concentrations.

Long-term stability of temocillin in dextrose 5% and in sodium chloride 0.9% polyolefin bags at 5 ± 3°C after freeze-thaw treatment.

INTRODUCTION: The aim of this study was to investigate the stability of a mixture of temocillin 20mg/ml in 5% dextrose and in 0.9% sodium chloride polyolefin bags after freezing, microwave thawing and long-term storage at 5±3°C. METHODS: The stability of ten polyolefin bags containing 20mg/ml of temocillin, five bags in 5% dextrose and five bags in 0.9% sodium chloride, prepared under aseptic conditions was studied after freezing for 1 month at -20°C, thawing in a microwave oven with a validated cycle, and stored at 5±3°C. Over 30 days, temocillin concentrations were measured by high-pressure liquid chromatography. Visual inspections, microscope observation, spectrophotometric measurements and pH measurements were also performed. RESULTS AND DISCUSSION: No precipitation occurred in the preparations but minor colour change was observed. No microaggregate was observed with optical microscopy or revealed by a change of absorbance. Based on a shelf life of 95% residual potency, temocillin infusions were stable at least 11 days in 5% dextrose and 14 days in 0.9% sodium chloride after freezing and microwave thawing (corresponding at the period where 95% lower confidence limit of the concentration-time profile remained superior to 95% of the initial concentration). During this period, the pH values of drug solutions have been observed to decrease without affecting chromatographic parameters. CONCLUSION: Within these limits, temocillin in 5% dextrose and in 0.9% sodium chloride infusions may be prepared and frozen in advance by a centralized intravenous admixture service then thawed before use in clinical units.

Integral assessment of pollution in the Suquía River (Córdoba, Argentina) as a contribution to lotic ecosystem restoration programs.

The Suquía River lower-middle basin (Córdoba, Argentina) is subject to a strong anthropic impact because it receives pollutants from different sources (industries, wastewaters, heavy traffic, agricultural land use, etc.) We have assessed the degree of watershed degradation of Suquía River lower-middle sections through the analysis of different ecosystem compartments (air, water, riparian soil, sediments and biota), in order to provide useful data to be considered in future river restoration programs. Four study sites were selected along the river (La Calera city, Córdoba city, Corazón de María village and Río Primero city) which were sampled during the low- and high-water flow periods. We analyzed: a) chemical and physical characteristics of water, sediments, and riparian soil; b) heavy metal content of water and sediments, and c) semi-volatile organic compounds in air. Besides, pollutant bioindicators such as fish assemblages, lichens (Usnea amblyoclada), vascular plants (Tradescantia pallida), and microorganisms (fecal coliform and Escherichia coli) were used to further assess the status of the river. All analyzed ecological compartments were affected by water pollution, particularly, fish assemblages, sediments and riparian soils by heavy metal and coliform bacteria. Moreover, we detected a possible contribution of sulfur and a high pollutant content in air that merit further research about other air-water exchanges. Accordingly, we strongly suggest that an action to restore or remediate the anthropic effect on the Suquía River be extended to all possible compartments along the river.

Physico-chemical analysis of several injectable drug in ready-to-use infusion after microwave freeze-thaw treatment and final storage at 5 ± 3 °C.

OBJECTIVE: In hospitals, the majority of the reconstitution of injectable drugs are carried out right before the administration to the patient by the nursing staff. The risks and errors related on their preparation and administration are numerous. The standardization, the centralization of these preparations and reconstitution by the hospital pharmacy make it possible to reduce the various risks and errors To enhance the number of drugs taken in charge, it is necessary to develop the long-term stability of ready-to-use drugs. Freezing seems an easy method but defrosting takes too much time. Some authors develop the concept of microwave treatment and apply this to different drugs. A characteristic of these studies was nevertheless the short period of study after thawing. METHODS: Long-term stability studies were started for different drugs mainly used in the hospital, and verify their stability after freezing at temperature<- 25°C, long-term storage (1 to 4 months), microwave-thawing and long-term storage at 5 ± 3°C. RESULTS: Sixteen molecules were tested and preserve more than 90% of their initial concentration the day of defrosting by microwave oven like this value a certain number of days at 5 ± 3°C. All the analyses were carried out by HPLC. CONCLUSION: The microwave freeze/thawing treatment allows the production of more important batches, makes profit of this technique in workload and material beyond a certain produced quantity. The described results encourage to check the possibilities of taking in charge other molecules regularly used in the Hospital Institutions.

Long-term stability of the hydrochlorides of tramadol and alizapride in dextrose 5% polyolefin bag at 5+/-3 degrees C.

OBJECTIVE: To investigate the stability of tramadol hydrochloride 100mg associated with alizapride 50mg in 100ml of 5% dextrose solution stored at 5+/-3 degrees C. METHODS: Solutions of 5% dextrose 100ml in polyolefin bags (n=5) containing approximately tramadol hydrochloride 100mg associated with alizapride 50mg were prepared under aseptic conditions and stored about 32 days at 5+/-3 degrees C. The tramadol hydrochloride and alizapride concentrations were measured by high-performance liquid chromatography (HPLC). Visual inspection was performed and pH was measured periodically during the storage. Stability of the solutions was defined as the common regression line 95% lower confidence limit of the concentration remaining superior to 90% of the initial concentration as recommended by the Food and Drug Administration (FDA). RESULTS: No color change or precipitation in the solutions was observed. Tramadol hydrochloride 100mg associated with alizapride 50mg in 100ml of 5% dextrose infusions was stable when stored at 5+/-3 degrees C during 32 days. Throughout this period, the lower confidence limit of the estimated regression line of concentration-time profile remained above 90% of the initial concentration. There was no significant change in pH during storage. CONCLUSION: Under the conditions of this study, tramadol hydrochloride 100mg associated with alizapride 50mg in 100ml of 5% dextrose infusions stored up to 32 days at 5+/-3 degrees C remain stable and may be prepared in advance by a Centralized Intravenous Additive Service (CIVAS) to improve safety and management.

Effect of freezing, long-term storage and microwave thawing on the stability of a mixture of diclofenac and sodium bicarbonate in glucose 5% polyolefin bags.

OBJECTIVE: Preparation in advance of intravenous solution could be efficient to improve quality assurance, security, time management and cost saving of drug delivery. The aim of this study was to investigate the stability of a mixture of diclofenac 75 mg/100 ml and sodium bicarbonate 42 mg/100 ml in 5% glucose polyolefin bags after freezing, long-term storage, and microwave thawing. METHOD: The stability of five polyolefin bags containing approximately 75 mg/100ml of diclofenac and 42 mg/100ml of sodium bicarbonate in 5% glucose prepared under aseptic conditions was studied after freezing for 2 months at -20 degrees C, thawing in a microwave oven with a validated cycle, and stored at 5 + or - 3 degrees C. Diclofenac concentrations were measured by high-pressure liquid chromatography using a reversed-phase column, a mobile phase consisting of 40% of acetonitrile (v/v) in KH(2)PO(4) buffer 0.02 M, pH 8.40 + or - 0.05, and UV detection at 276.0 nm. Visual inspection, microscope observation, spectrophotometric measurements and pH measurement were also performed. RESULTS: No colour change or precipitation occurred in the preparations. No microaggregate was observed with optical microscopy or revealed by a change of absorbance. Based on a shelf-life of 90% residual potency, diclofenac was stable for at least 30 days after freezing and microwave thawing, period where 95% lower confidence limit of the concentration-time profile remained superior to 90% of the initial concentration. During this period, the pH values of drug solutions have not been altered. CONCLUSION: Within these limits, diclofenac in 5% glucose infusion may be prepared and frozen in advance by a centralized intravenous admixture service, then thawed before use in clinical units.