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Author
Argemí Gil, Anna
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Abstract
In the aftermath of the recent COVID-19 pandemic, there have been significant changes in hospital care, with the goal of increasing resources to promote home hospitalization (HDOM). This allows the patient to receive treatment at home as an alternative to traditional hospitalization.
This work investigates the stability of medications generally administered to patients in the HDOM unit of the Hospital Clinic of Barcelona (HCB), in order to ensure that their effectiveness is not com-promised when administered at home.
This project's main goal is to assess the physical and chemical stability of β-lactam antibiotics com-monly used by HDOM.
Meropenem, Imipenem, Cilastatin, Ceftazidime, Avibactam Ceftaroline fosamil, and Cefiderocol are the seven drugs studied in this work. They have complex and polar structures with a wide range of pKa, which adds to the design of the analytical procedures a challenge.
For the drugs in study, four UHPLC-DAD methods have been developed.
A first method was used to determine the most apolar analytes (Meropenem, Cilastatin, Cefta-zidima, Ceftaroline fosamil, and Cefiderocol) using two reverse phase orthogonal columns (BEH C18 and CSH-Phenyl Hexil) and as an eluent methanol / water with trifluoroacetic acid added as an additive to reach pH 2.
The second method determines Imipenem, which is complex due to its high polarity, using an HILIC type phase column (BEH Amide) and acetonitrile with 5% isopropanol and 5 mM ammonium acetate as mobile phase at pH 6 (30:70), achieving good retention of the analyte at low water content.
Finally, the third method successfully preserves Ceftaroline fosamil with good peak symmetry. A re-verse phase column with a combined substituent (Luna Omega Polar C18) and a 0,1 percent HCOOH acid medium with methanol as the organic modifier are used to achieve this.
The stability of APIs in saline drugs has been determined using the methods developed. Except for Imipenem, which has a 78 percent recovery rate under these conditions, all have been found to be stable for 24 hours when kept cold. As a result, the sample in injectable solution prepared in Viaflo® of this antibiotic is studied for 96 hours, simulating the specific preparation carried out by the Phar-macy Service of the Hospital Clinic of Barcelona and its conservation in the patient's home conditions, obtaining that Imipenem is only stable (R> 90%) for 9 hours as long as the controlled temperature is kept below 5oC.
The impurities in the drugs under study were identified by mass spectrum using a UHPLC-QTOF sys-tem. The evolution of the impurities formed during the degradation of Imipenem in the sample has also been studied using the MetabolitePilot software.
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