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The microtiter plate ALT assay is helpful in allowing the simultaneous distribution of ALT and immunoenzymatic assays. It provides accurate results and a minimal risk of false-negative results.

BackgroundVoriconazole is an antifungal agent effective on most keratitis causative fungi with an excellent transcorneal penetration. Voriconazole eyedrops (VED) are unavailable in Europe and are usually compounded in hospital pharmacies. New eyedrop containers emerged on the hospital market (eg, high density polyethylene bottles available in trays (CAT)) for which few stability data are available, or Novelia bottles which innovative insert maintains sterility after opening (no stability data available).PurposeTo collect data on VED stability in 3 different containers in order to switch if necessary: amber glass, HPDE bottles and Novelia bottles stored frozen (−20°C) and refrigerated once thawed.Material and methods3 batches of 1% VED (10 mL) were aseptically compounded under a laminar flow hood from injectable Vfend (Pfizer) and sterile water for injection (Baxter), and stored at −20°C in amber glass (n=32; Gravis), HDPE (n=32; CAT) or Novelia (n=31; Nemera) bottles. The stability study was done according to the GERPAC-SFPC stability study guidelines. At each time point, the visual aspect was checked and voriconazole concentration (using a stability indicating HPLC-UV-diode array detector method), pH and osmolality were measured. Non-visible particle counts (by light obscuration particle count test), sterility and absence of racemisation (impurity D–(2S,3R)-voriconazole–detected by chiral HPLC) were assessed at the beginning and end of the study. Parameters were measured: when stored for 3 months at −20°C; then thawed, after 15 days at +2 to +8°C, with comparison of two thawing methods (+2 to +8°C for 6 hours or 25°C for 2 hours). Statistical analysis were performed using non-parametric tests (α < 5%) to compare containers.ResultsDuring storage, the concentration was between 95.2±1.4% and 103.6±1.3% of the initial concentration (Co) (NS); 15 days after thawing, the concentration was between 97.1±1.6% and 98.6±0.8% of Co (NS). pH remained stable (NS). Osmolality was slightly higher in glass than in plastic containers (p=0.003). Sterility was preserved. Count of ≥10 µm particles remained <80/mL. Degradation product areas increased by a maximum of 1.45 and remained unquantifiable. No impact of the thawing method was evidenced. Impurity D was not detected.ConclusionVED remained stable for up to 3 months at −20°C and for 15 days after thawing, with no notable difference between the three containers, allowing us to choose the most suitable.No conflict of interest

BackgroundVoriconazole is a triazole antifungal agent effective in most cases of keratitis caused by fungi. Off-label use of extemporaneously compounded intraocular (intrastromal, intracameral) voriconazole has shown promising results in deep fungal ophthalmic infections, and abscessed, recurrent or drug resistant eye infections. Stability data on voriconazole intraocular solutions (VIS) are lacking.PurposeTo assess the stability of 50 and 100 µg/0.1mL VIS stocked at 2–8°C.Material and methods2 batches of VIS (2 mL; 1 batch per concentration) were aseptically compounded from injectable Vfend (Pfizer) and Ringer’s lactate solution (Baxter), stored at 2–8°C in 3 part syringes (n=66) and analysed on day 13 (D13) and after 1 (D30) and 1.5 (D44) months. Stability study was led according to the GERPAC-SFPC stability studies guidelines. At each time point, visual aspect was checked, and voriconazole relative concentration (% of initial concentration, using a stability indicating HPLC-UV-diode-array-detector method), pH and osmolality were measured. Non-visible particle counts (using light obscuration particle count test) for particle size ≥ 10 µm and ≥25 µm (Eur Pharm 2.9.19 threshold: 6000 and 600/recipient, respectively) and sterility were assessed. Statistical analysis was carried out using non-parametric tests (α <5%). Degradation rates were compared with a Student t test.ResultsFor every time point, CI relative concentrations were (0.993; +infinite (and) 0.951; +infinite (respectively, for 50 and 100 µg/0.1 mL), and remained superior to 95% (p<0.0001). No difference was shown in degradation rates (0.008±0.120 and −0.231±0.961 (p=0.497)) between the 2 concentrations, indicating no concentration effect. Osmolality remained stable (from 281.2 (T0) to 282.2 (D44) and from 298.2 to 299.8 mOsm/kg (p=0.490)). pH increased from 6.78 (T0) to 7.11 (D44) (p=0.150). Particles size ≥ 10 µm rose from 240.3 (D13) to 339.1 (D44) and from 363.2 to 487.6 particles/syringe, respectively, for 50 and 100 µg/0.1 mL. Particles size ≥ 25 µm rose on D13 from 3.3 to 4.4 and from 5.2 to 6.9 particles/syringe respectively. For voriconazole degradation products, whose toxicity is unknown, areas increased by a maximum of 1.3 (D13) and 2 (D44), remaining unquantifiable. Sterility was preserved to at least D13 with no change in visual aspect.ConclusionVIS remained stable for 13 days at 2–8°C. We advise a shelf-life of a maximum of 13 days for both VIS kept at 2–8°C.No conflict of interest