[Show abstract][Hide abstract] ABSTRACT: Tramadol is a centrally acting opioid analgesic structurally related to codeine and morphine. Analogs of tramadol with deuterium-for-hydrogen replacement at metabolically active sites were prepared and evaluated in vitro and in vivo.
[Show abstract][Hide abstract] ABSTRACT: A new ion trap scan function for gas chromatography/mass spectrometry (GC/MS) quantitation is described that employs alternating
mass-selective storage (rf/dc isolation) of ions from an analyte and its coeluting isotopically labeled internal standard.
This scan includes two separate ionization/isolation/mass analysis sequences within the same scan function, each optimized
for either the analyte or the internal standard. This results in alternating between analyzing the analyte and the internal
standard during their coelution. The method is conceptually similar to using two different scan functions to analyze either
the analyte or the internal standard in alternating scans; however, it is much faster because it eliminates the slow procedure
of continuously downloading alternating scan functions from disk. This allows more data points to be obtained over a GC peak,
resulting in more reproducible GC peak profiles as well as better sensitivity and precision. Results of calibration curves
spanning four orders of magnitude (0.5 pg to 5 pg injected on column) obtained by using this method give excellent linear
2 > 0.9990) and precision (relative standard deviations of triplicate injections < 10%).
Full-text · Article · Jan 1992 · Journal of the American Society for Mass Spectrometry
[Show abstract][Hide abstract] ABSTRACT: A rapid, sensitive gas chromatographic head-space method was developed for assay of biologic fluids for formic acid by its conversion to methyl formate. The flame ionization detector employed was sensitive to about 0.5 mg/liter formic acid and linear to at least 1000 mg/liter. The coefficient of variation was 6% or less from 5 to 1000 mg/liter. The method has potential application to methanol poisoning.
No preview · Article · May 1980 · Biochemical Medicine
[Show abstract][Hide abstract] ABSTRACT: An 18-yr-old male with a severe ethchlorvynol (ECV) overdose was treated with Amberlite XAD-4 resin hemoperfusion. Plasma ECV concentrations declined 33% during a 3.5-hr hemoperfusion, but rebounded substantially, peaking 6 hr later. It was estimated that 16% of ECV in the body was removed. Following hemoperfusion, plasma ECV concentrations declined linearly at a rate of 13 mg/l/day. Hemoperfusion clearance was estimated by both the traditional method, using extraction ratios across the column and column blood flow (CI =270 ml/min), and an alternative method, using blood concentrations during hemoperfusion and recovery of drug from the resin (CI = 184 ml/min). The latter may provide a better estimate of hemoperfusion clearance because it is not subject to error (which can be substantial) in measurement of column blood flow. The resin completely extracted ECV from plasma, resulting in a rate of elimination 10 times that expected from endogenous processes. To aid in kinetic analysis, blood:plasma partition and protein binding of ECV in 3 normal subjects were also examined. Blood:plasma ratio averaged 0.88 0.04 and fraction free in plasma, 0.38 0.02; neither changed as a function of blood concentration between 27 and 108 mg/l. Our data indicate that removal of ECV from the overdosed patient by hemoperfusion is limited by extensive distribution in and slow redistribution from body tissues, but because of the extremely slow rate of removal by the body and the severe nature of the ECV overdose, Amberlite XAD-4 hemoperfusion may be clinically useful.
[Show abstract][Hide abstract] ABSTRACT: Previous in situ studies showed that intestinal drug absorption is strongly influenced by intestinal pH. Three animal species considered for bioavailability testing were studied in situ to determine intestinal pH. Results from the rat and dog correlated well with results in humans, while results from the rabbit did not. The rabbit appears to be a poor candidate for attempted animal-human bioavailability correlations.
No preview · Article · Oct 1975 · Journal of Pharmaceutical Sciences
[Show abstract][Hide abstract] ABSTRACT: (R,R)-Formoterol, a highly selective, potent and long-acting β2-adrenoceptor agonist, is primarily metabolized to phenolic (M1) and benzylic (M2) glucuronides in man. The glucuronidation of formoterol enantiomers with 12 cDNA-expressed SUPERSOMES (Baculovirus/Insect cell system) and human liver microsomes (HLM) are reported. Incubations of either (R,R)- and (S,S)-formoterol with HLM produced two glucuronide metabolites (M1 and M2). The apparent Km and Vmax of the (R,R)- and (S,S)-formoterol metabolite M1 in HLM were 1410 and 864 µM and 788 and 2216 pmol/mg/min, respectively. For (R,R)-formoterol, UGT2B17 was the most active cDNA-expressed human UGT isozyme followed by 1A9, 2B7 and 1A1 in decreasing order of activity. UGT1A1 was the most active isozyme studied for (S,S)-formoterol glucuronidation. The in vitro glucuronidation of both (R,R)- and (S,S)-formoterol (M1+M2) was inhibited by bilirubin, a chemical inhibitor and a substrate specific for UGT1A1, indicating some involvement of UGT1A1 in the reaction. Despite substantial quantitative and qualitative differences in glucuronidation activity, (R,R)- and (S,S)-formoterol were found to be substrates for most of the UGT isozymes examined. Support for this study was provided by Sepracor Inc., Marlborough, MA.