AN HPLC AND 1H NMR STUDY OF THE CYTARABINE DEGRADATION IN CLINICAL CONDITIONS TO AVOID DRUG WASTE, DECREASE THERAPY COSTS AND IMPROVE PATIENT COMPLIANCE
(Abstract release date: 05/19/16)
EHA Library. Cerchione C. 06/09/16; 135009; PB2109
Dr. Claudio Cerchione
Contributions
Contributions
Abstract
Abstract: PB2109
Type: Publication Only
Background
Cytarabine, the 4-Amino-1-(β-D-arabinofuranosyl)-2(1H)-pyrimidinone, (ARA-C), is an antimetabolite cytidine analogue used worldwide as key drug in the management of leukaemia. As specified in the manufacturers’ instructions, once the components – sterile water and ARA-C powder – are unpackaged and mixed, the solution begins to degrade after 6 hours at room temperature and 12 hours at 4 °C.
Aims
To evaluate how to avoid wasting the drug in short-term low dose treatment regimens, the reconstituted samples, stored in the dark at 25° and 4° C, were analyzed every day of the test week by reversed phase high-performance liquid chromatography (RP-UHPLC) and high-field nuclear magnetic resonance spectroscopy (1H NMR).
Methods
All the samples remained unchanged for the entire week, which corresponds to the time required to administer the entire commercial drug package during low-dose therapeutic regimens. The drug solution was stored in a glass container at 4 °C in an ordinary freezer and drawn with sterile plastic syringes; during this period, no bacterial or fungal contamination was observed. After one month, the samples presented evidence of a degradation product (0.8% of starting material), identified as 1-(β-D-arabinofuranosyl)-pyrimidine-2,4-(1H,3H)-dione (ARA-U).
Results
Our findings provide evidence of an optimal physico-chemical stability and microbiological sterility of ARA-C solution stored for one week in the dark, at 4°C. This encourages the use of the reconstituted drug for the time required for short-term multi-dose treatments, avoiding drug waste, patient stress and hospital crowding. Moreover, it seems possible to leave in the same container surplus of different ARA-C packages, improving the cost-effectiveness of the treatment without affecting its efficacy and safety. An additional advantage is the fact that patients are able to have the treatment administered at home.
Conclusion
Our results show that a solution of reconstituted ARA-C could be employed for a longer period that what suggested by the manufacturers. In fact, patients could receive a safe aliquot to be used at home for short-term treatments, thus optimizing the use of aliquot residues and avoiding vial manipulation and the production of special waste material.
Session topic: E-poster
Type: Publication Only
Background
Cytarabine, the 4-Amino-1-(β-D-arabinofuranosyl)-2(1H)-pyrimidinone, (ARA-C), is an antimetabolite cytidine analogue used worldwide as key drug in the management of leukaemia. As specified in the manufacturers’ instructions, once the components – sterile water and ARA-C powder – are unpackaged and mixed, the solution begins to degrade after 6 hours at room temperature and 12 hours at 4 °C.
Aims
To evaluate how to avoid wasting the drug in short-term low dose treatment regimens, the reconstituted samples, stored in the dark at 25° and 4° C, were analyzed every day of the test week by reversed phase high-performance liquid chromatography (RP-UHPLC) and high-field nuclear magnetic resonance spectroscopy (1H NMR).
Methods
All the samples remained unchanged for the entire week, which corresponds to the time required to administer the entire commercial drug package during low-dose therapeutic regimens. The drug solution was stored in a glass container at 4 °C in an ordinary freezer and drawn with sterile plastic syringes; during this period, no bacterial or fungal contamination was observed. After one month, the samples presented evidence of a degradation product (0.8% of starting material), identified as 1-(β-D-arabinofuranosyl)-pyrimidine-2,4-(1H,3H)-dione (ARA-U).
Results
Our findings provide evidence of an optimal physico-chemical stability and microbiological sterility of ARA-C solution stored for one week in the dark, at 4°C. This encourages the use of the reconstituted drug for the time required for short-term multi-dose treatments, avoiding drug waste, patient stress and hospital crowding. Moreover, it seems possible to leave in the same container surplus of different ARA-C packages, improving the cost-effectiveness of the treatment without affecting its efficacy and safety. An additional advantage is the fact that patients are able to have the treatment administered at home.
Conclusion
Our results show that a solution of reconstituted ARA-C could be employed for a longer period that what suggested by the manufacturers. In fact, patients could receive a safe aliquot to be used at home for short-term treatments, thus optimizing the use of aliquot residues and avoiding vial manipulation and the production of special waste material.
Session topic: E-poster
Abstract: PB2109
Type: Publication Only
Background
Cytarabine, the 4-Amino-1-(β-D-arabinofuranosyl)-2(1H)-pyrimidinone, (ARA-C), is an antimetabolite cytidine analogue used worldwide as key drug in the management of leukaemia. As specified in the manufacturers’ instructions, once the components – sterile water and ARA-C powder – are unpackaged and mixed, the solution begins to degrade after 6 hours at room temperature and 12 hours at 4 °C.
Aims
To evaluate how to avoid wasting the drug in short-term low dose treatment regimens, the reconstituted samples, stored in the dark at 25° and 4° C, were analyzed every day of the test week by reversed phase high-performance liquid chromatography (RP-UHPLC) and high-field nuclear magnetic resonance spectroscopy (1H NMR).
Methods
All the samples remained unchanged for the entire week, which corresponds to the time required to administer the entire commercial drug package during low-dose therapeutic regimens. The drug solution was stored in a glass container at 4 °C in an ordinary freezer and drawn with sterile plastic syringes; during this period, no bacterial or fungal contamination was observed. After one month, the samples presented evidence of a degradation product (0.8% of starting material), identified as 1-(β-D-arabinofuranosyl)-pyrimidine-2,4-(1H,3H)-dione (ARA-U).
Results
Our findings provide evidence of an optimal physico-chemical stability and microbiological sterility of ARA-C solution stored for one week in the dark, at 4°C. This encourages the use of the reconstituted drug for the time required for short-term multi-dose treatments, avoiding drug waste, patient stress and hospital crowding. Moreover, it seems possible to leave in the same container surplus of different ARA-C packages, improving the cost-effectiveness of the treatment without affecting its efficacy and safety. An additional advantage is the fact that patients are able to have the treatment administered at home.
Conclusion
Our results show that a solution of reconstituted ARA-C could be employed for a longer period that what suggested by the manufacturers. In fact, patients could receive a safe aliquot to be used at home for short-term treatments, thus optimizing the use of aliquot residues and avoiding vial manipulation and the production of special waste material.
Session topic: E-poster
Type: Publication Only
Background
Cytarabine, the 4-Amino-1-(β-D-arabinofuranosyl)-2(1H)-pyrimidinone, (ARA-C), is an antimetabolite cytidine analogue used worldwide as key drug in the management of leukaemia. As specified in the manufacturers’ instructions, once the components – sterile water and ARA-C powder – are unpackaged and mixed, the solution begins to degrade after 6 hours at room temperature and 12 hours at 4 °C.
Aims
To evaluate how to avoid wasting the drug in short-term low dose treatment regimens, the reconstituted samples, stored in the dark at 25° and 4° C, were analyzed every day of the test week by reversed phase high-performance liquid chromatography (RP-UHPLC) and high-field nuclear magnetic resonance spectroscopy (1H NMR).
Methods
All the samples remained unchanged for the entire week, which corresponds to the time required to administer the entire commercial drug package during low-dose therapeutic regimens. The drug solution was stored in a glass container at 4 °C in an ordinary freezer and drawn with sterile plastic syringes; during this period, no bacterial or fungal contamination was observed. After one month, the samples presented evidence of a degradation product (0.8% of starting material), identified as 1-(β-D-arabinofuranosyl)-pyrimidine-2,4-(1H,3H)-dione (ARA-U).
Results
Our findings provide evidence of an optimal physico-chemical stability and microbiological sterility of ARA-C solution stored for one week in the dark, at 4°C. This encourages the use of the reconstituted drug for the time required for short-term multi-dose treatments, avoiding drug waste, patient stress and hospital crowding. Moreover, it seems possible to leave in the same container surplus of different ARA-C packages, improving the cost-effectiveness of the treatment without affecting its efficacy and safety. An additional advantage is the fact that patients are able to have the treatment administered at home.
Conclusion
Our results show that a solution of reconstituted ARA-C could be employed for a longer period that what suggested by the manufacturers. In fact, patients could receive a safe aliquot to be used at home for short-term treatments, thus optimizing the use of aliquot residues and avoiding vial manipulation and the production of special waste material.
Session topic: E-poster
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