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Purification of Triamcinolone Acetonide Suspension for Intravitreal Use
Author Response: Purification of Triamcinolone Acetonide Suspension for Intravitreal Use
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Enrique Soto-Pedre
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esoto{at}eibi.es Enrique Soto-Pedre
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We read with interest the article by M.E. Hartnett and co-workers.1 They report that "[c]entrifugation was chosen as the desired purification technique" for purification of triamcinolone acetonide suspension for intravitreal injection. We very much appreciate that they have chosen our method (i.e., the centrifugation for 5 minutes with extraction of the supernatant and the pellet resuspension with saline solution). We think this paper is interesting, but needs further clarification of the real source of the chosen purification technique that seems to be granted to García-Arumí et al.2 by the authors. As far as we know, the centrifugation technique described by García-Arumí et al. was first reported by Hernaez-Ortega in the year 20033 and first published by Hernaez-Ortega and me in the 2004 July/August issue of the journal Ophthalmic Surgery, Lasers & Imaging4; and it was further developed 2 years later to describe the results of a gas chromatographic procedure that had been developed to determine quantities of benzyl alcohol in the commercially available injectable formulation of triamcinolone acetonide containing benzyl alcohol as a preservative.5 In fact, we are grateful to the editor-in-chief of the British Journal of Ophthalmology who agreed to publish our letter to make things more clear.6 Besides, the term "purification" had been first applied to the removal of most of the vehicle from a commercially available triamcinolone acetonide suspension by us. The authors state in the methods section that the pellet was resuspended with 1 ml of phosphate-buffered saline (PBS) after centrifugation. However, the pellet resuspension with 0.9 ml of balanced salt solution (BSS) was finally recommended by García-Arumí et al. as we had previously pointed out in our papers. This issue needs to be explained. We encourage the authors to clarify the above-mentioned issues. Such clarifications will help reduce misleading understanding of the purification method of triamcinolone acetonide suspension for intravitreal use by means of a centrifuge. Enrique Soto-Pedre and Maria Concepcion Hernaez-Ortega European Innovative Biomedicine Institute (EIBI), Cantabria, Spain. References 1. Hartnett ME, Martiniuk DJ, Saito Y, Geisen P, Peterson LJ, McColm JR. Triamcinolone reduces neovascularization, capillary density and IGF-1
receptor phosphorylation in a model of oxygen-induced retinopathy. Invest Ophthalmol Vis Sci. 2006;47:4975-4982. |
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M. Elizabeth Hartnett
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hartnet{at}med.unc.edu M. Elizabeth Hartnett
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We thank Drs. Soto-Pedre and Hernaez-Ortega for their interest in our article1 and in bringing forth the need for clarification in the technique for purifying triamcinolone acetonide (TA) for intraocular use. As our methods explain, we re-suspended stock TA (40 mg/mL) with enough 1 M phosphate-buffered saline (PBS) to achieve four different concentrations (6 mg/mL, 15 mg/mL, 30 mg/mL, and 60 mg/mL) for intravitreous injection. For example, to prepare a sufficient quantity of 30 mg/mL TA for the treatment of 1 litter, 20 mL stock TA was centrifuged for 5 minutes and the supernatant was removed. The drug pellet was then reconstituted with 26.6 mL PBS to produce the desired concentration of 30 mg/mL. To prepare 60 mg/mL TA, 40 mL stock TA was centrifuged for 5 minutes and the supernatant was removed. This drug pellet was then reconstituted with 26.6 mL PBS to produce the desired concentration of 60 mg/mL. The method we used for removing the potentially toxic drug vehicle seems to be in line with the published article by these authors in Ophthalmic Surgery and Laser Imaging,2 as they indicate. We apologize that we did not include this reference in our original paper as the paper by García-Arumí et al.3 made no mention of this work. Thank you again for this clarification pertaining to the TA preparation technique used in our study. We appreciate the helpful comments by Drs. Soto-Pedre and Hernaez-Ortega as they have no doubt contributed to the integrity of our work. David J. Martiniuk Department of Ophthalmology, University of North Carolina, Chapel Hill, NC References
1. Hartnett ME, Martiniuk DJ, Saito Y, Geisen P, Peterson LJ, McColm JR. Triamcinolone reduces neovascularization, capillary density and IGF-1 receptor phosphorylation in a model of oxygen-induced retinopathy. Invest Ophthalmol Vis Sci. 2006;47:4975-4982. |
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