Mass fragmentographic detection of normorphine in urine of man after codeine intake

✍ Scribed by Wilhelm O. R. Ebbighausen; John Mowat; Per Vestergaard

• Publisher: John Wiley and Sons
• Year: 1973
• Tongue: English
• Weight: 337 KB
• Volume: 62
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600620133

✦ Synopsis

with the structurally similar 4-biphenylyl N-methylcarbarnate ( I , 2) indicated that kou-in water was six times that of the value in 50% ethanol. Thus, it may reasonably be predicted from the data in Table I that considerable hydrolysis of I would occur over tlie pH range encountered in the small intestine and that absorption of the intact drug could be variable from dose to dose. In addition, noncnzymatic hydrolysis at the pH of the blood, following absorption, would be rapid. The half-life of I at pH 7.3, 37", calculated from the data in Table I is 73 min. Comparison of these results with those obtained earlier with 4-biphenylyl N-methylcarbarnate ( I ) indicates that substitution of the 4-benzoyl group for the 4-phenyl group increases the hydrolysis rate nearly 2OO-fold.

Foliowing oral administration of I to the dog, traces of intact 1 were detected in the urine but were below the level of reasonable quantification (<0.1 of the dose). The only drug-related materials detected in the urine were the hydrolysis product, 11, and glucuronidc and/or sulfate conjugates of I1 (Table TI). Overall excretion ranged from 8.7 to 17.3% of the dose in the two experiments.

These results are consistent with erratic absolption and the predicted extensive hydrolysis of1 based on the in cirro kinetic studies.

Urinary excretion of 47-92% of orally administered I1 as a glucuronide conjugate in the rabbit was reported by Robinson (5). The present results for I1 (produced from I) in the dog are qualitatively similar.