Influence of medium and temperature on the hydrolysis kinetics of propacetamol hydrochloride: determination using derivative spectrophotometry.
Propacetamol hydrochloride (PRO) is a water-soluble prodrug of paracetamol (PA) which can be parenterally administered as analgesic for the treatment of postoperative pain, acute trauma, and gastric and/or intestinal disorders where oral administration is not possible. In these circumstances, PRO can be administered in physiologic or glucose solutions since it is rapidly and quantitatively hydrolyzed into PA by plasma estearases. We have studied the degradation kinetics of PRO in 5% glucose and 0.9% saline solutions at 4 degrees C and 25 degrees C (storage and room temperatures, respectively). The analytic technique used to determine PRO and PA quantitatively was first-derivative spectrophotometry. The degradation process of PRO can be best fitted to a second-order kinetics with independence of the medium used (saline or glucose solution). The hydrolysis kinetics of PRO conversion into PA depends on the temperature but not on the assay medium (saline or glucose solution). The degradation rate constants obtained for PRO were approximately 4.5 times higher at 25 degrees C than at 4 degrees C. The values of t(90%) for PRO were 3.17 h and 3.61 h at 25 degrees C, and 13.42 h and 12.36 h at 4 degrees C when the tests were performed in 5% glucose and 0.9% saline solutions, respectively.
Barcia
Emilia
E
Department of Pharmaceutics, University Complutense of Madrid, School of Pharmacy, Spain. ebarcia@farm.ucm.es
Martin
Alicia
A
Azuara
Ma Luz
ML
Negro
Sofia
S
D000082:Acetaminophen / Q000494:pharmacology; D005947:Glucose / Q000737:chemistry; D006358:Hot Temperature; D006868:Hydrolysis; D007700:Kinetics; D011355:Prodrugs / Q000378:metabolism*; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet
D011355:Prodrugs; D012996:Solutions; D000082:Acetaminophen; D005947:Glucose