Stereoselective metabolic study of famprofazone

Abstract

Famprofazone (1) metabolites were studied in human urine after medication by 50 mg oral dose. The human urine was collected over 48 h from six volunteers at time intervals of 6, 12, 24 and 48 h. The amount of famprofazone metabolites were recovered from the urine samples by application of Extrelut extraction method. The resultant extracts were derivatized using N‐methyl‐N‐trimethylsilyltrifluoroacetamide (MSTFA) for trimethylsilylation followed by N‐methyl‐bis‐trifluoroacetamide (MBTFA) for trifluoroacetylation. Methamphetamine (2) and 3‐hydroxymethyl‐propyphenazone (3), excreted in human urine, were identified as famprofazone metabolites by gas chromatography–mass spectrometry (GC–MS). The quantitative results revealed that the average amounts of 2 and 3, excreted in human urine were equal to 2.6 and 4 mg, respectively, through 48 h. However, 3 was analysed after enzymatic hydrolysis of the urine samples using β‐glucuronidase/arylsulphatase. The excreted methamphetamine enantiomers could be separated by application of indirect GC‐technique using S‐(−)‐N‐trifluoroacetylprolyl chloride (TPC) as a chiral derivatizing agent. The average amount of (−)‐methamphetamine isomer excreted in the urine was found to be three fold those of the (+)‐isomer. © 1997 John Wiley & Sons, Ltd.

Interpreting methamphetamine levels in a high-use community

“…Famprofazone is an analgesic that is metabolized to Dand L-MA (5% to 14% of dose excreted as MA) (Cody 1996;Neugebauer et al 1997;Tseng et al 2007); however, it is not approved for use in the USA and is considered an insignificant contributor to the MA in the study (Hope 2010). Benzphetamine in the form of Didrex is prescribed for obesity (Cloyd 1997;Cody and Valtier 1998;Stafford and Radley 2003) Utilization of Benzphetamine in Oregon is considered low because its use is greater among those with health insurance, and Oregon Medicaid (health insurance) has not approved amphetamines for weight loss (Hope 2010).…”

Metabolic Profile of Famprofazone Following Multidose Administration

“…Several studies have shown famprofazone is metabolized to methamphetamine and amphetamine (2)(3)(4)(5) and both the d-and l-enantiomers are present (2,3). One study observed the excretion rate for the first 24 h in 3 subjects after a single 50mg dose (6).…”

Characterization and Determination of Major Bioactive Acids in Camel Urine Using Gas Chromatography Mass-spectrometry

“…3-hydroxymethyl-propyphenazone (3-OH-MP, m. wt. 246) was prepared in our laboratory by boiling, 1 g of 3-bromomethyl-propyphenazone in 50 ml water for 30 min [5] . The obtained crystals were washed with 0.1% sodium carbonate followed by water, filtered and dried over sodium hydroxide pellets in desiccators.…”