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Investigations into the physical and chemical stability of concentrated co-trimoxazole intravenous infusions


Khaleel, I and Zaidi, STR and Shastri, MD and Eapen, MS and Ming, LC and Wanandy, T and Patel, RP, Investigations into the physical and chemical stability of concentrated co-trimoxazole intravenous infusions, European Journal of Hospital Pharmacy pp. 1-7. ISSN 2047-9956 (2017) [Refereed Article]

Copyright Statement

Copyright 2017 European Association of Hospital Pharmacists (unless otherwise stated in the text of the article)

DOI: doi:10.1136/ejhpharm-2017-001225


Objectives: High dose of intravenous sulfamethoxazole and trimethoprim (co-trimoxazole) is often used in immunocompromised patients for the treatment of Pneumocystis jiroveci pneumonia. Current manufacturer’s dilution recommendation for intravenous co-trimoxazole (1:25 v/v) requires the administration of 2 L of additional fluid per day causing serious complications including pulmonary oedema. Intravenous administration of concentrated solution of co-trimoxazole may minimise the risk of fluid overload associated side effects. Therefore, the objective of the study was to investigate the physicochemical stability of concentrated intravenous co-trimoxazole solutions.

Methods: Four ampoules of intravenous co-trimoxazole were injected into an infusion bag containing either 480 (1:25 v/v), 380 (1:20 v/v), 280 (1:15 v/v) or 180 (1:10 v/v) mL of glucose 5% solution. Three bags for each dilution (total 12 bags) were prepared and stored at room temperature. An aliquot was withdrawn immediately (at 0 hour) and after 0.5, 1, 2 and 4 hours of storage for high-performance liquid-chromatography (HPLC) analysis, and additional samples were withdrawn every half an hour for microscopic examination. Each sample was analysed for the concentration of trimethoprim and sulfamethoxazole using a stability indicating HPLC method. Samples were assessed for pH, change in colour (visually) and for particle content (microscopically) immediately after preparation and on each time of analysis.

Results: Intravenous co-trimoxazole at 1:25, 1:20, 1:15 and 1:10 v/v retained more than 98% of the initial concentration of trimethoprim and sulfamethoxazole for 4 hours. There was no major change in pH at time zero and at various time points. Microscopically, no particles were detected for at least 4 hours and 2 hours when intravenous co-trimoxazole was diluted at 1:25 or 1:20 and 1:15 v/v, respectively. More than 1200 particles/ mL were detected after 2.5 hours of storage when intravenous co-trimoxazole was diluted at 1:15 v/v.

Conclusions: Intravenous co-trimoxazole is stable over a period of 4 hours when diluted with 380mL of glucose 5% solution (1:20 v/v) and for 2 hours when diluted with 280mL glucose 5% solution (1:15 v/v).

Item Details

Item Type:Refereed Article
Keywords:chromatography, stability, antibiotic, infusion, trimethoprim, sulfamethoxazole
Research Division:Biomedical and Clinical Sciences
Research Group:Pharmacology and pharmaceutical sciences
Research Field:Pharmaceutical sciences
Objective Division:Health
Objective Group:Public health (excl. specific population health)
Objective Field:Public health (excl. specific population health) not elsewhere classified
UTAS Author:Khaleel, I (Mrs Israa Khaleel)
UTAS Author:Zaidi, STR (Dr Tabish Razi Zaidi)
UTAS Author:Shastri, MD (Mr Madhur Shastri)
UTAS Author:Eapen, MS (Dr Mathew Eapen)
UTAS Author:Ming, LC (Dr Long Ming)
UTAS Author:Wanandy, T (Mr Troy Wanandy)
UTAS Author:Patel, RP (Dr Rahul Patel)
ID Code:119067
Year Published:2017
Web of Science® Times Cited:5
Deposited By:Pharmacy
Deposited On:2017-07-25
Last Modified:2022-07-01

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