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Laboratory and Animal Investigations |

Degradation of Histamine Solutions Used for Bronchoprovocation*

Patricia Marshik, PharmD; Siyawosh Moghaddam, PhD; Ian Tebbett, PhD; Leslie Hendeles, PharmD
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*From the College of Pharmacy, University of Florida, Gainesville, FL.



Chest. 1999;115(1):194-199. doi:10.1378/chest.115.1.194
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Study objectives: To determine optimal storage conditions for histamine diphosphate (HDP) solutions used for bronchoprovocation.

Design: HDP was dissolved in buffered saline solution to concentrations of 0.125 to 16 mg/mL and stored in 3-mL unit dose syringes at different temperatures for varying lengths of time, with and without protection from fluorescent light.

Setting: Dark freezer (−20°C), dark refrigerator (4°C), and laboratory counter top (20°C) illuminated by fluorescent light (375 foot-candles).

Measurements: HDP concentrations were measured after the solutions were prepared and during storage by a high-performance liquid chromatographic assay that differentiates histamine from its break down products.

Results: All dilutions were sterile after preparation and contained 97 to 110% of the labeled amount of HDP. Solutions constantly exposed to fluorescent light (375 foot-candles) and room temperature (20°C) contained only 20 to 37% of the initial concentrations after 7 days. The same dilutions stored at room temperature, but protected from light, contained 83 to 94% of the initial concentrations. Dilutions stored in the dark in a refrigerator (4°C) retained 97% of the initial concentrations after 8 weeks, while dilutions stored in the dark freezer (−20°C) were stable for 12 months.

Conclusions: Exposure to fluorescent light at room temperature results in degradation of histamine solutions used for bronchoprovocation. Dilutions stored in unit dose syringes and protected from light are stable for at least 8 weeks in the refrigerator and up to 12 months frozen. Once removed from the refrigerator or freezer, the solutions should be used within 6 h or discarded.

Abbreviations: FDA = Food and Drug Administration; HDP = histamine diphosphate; HPLC = high-performance liquid chromatography

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