Determination of morphine, morphine-3-glucuronide and (tentatively) morphine-6-glucuronide in plasma and urine using ion-pair high-performance liquid chromatography

Svensson, Jan‐Olof; Rane, Anders; Säwe, Juliette; Sjöqvist, Folke

doi:10.1016/s0378-4347(00)80494-6

Cited by 269 publications

(80 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Morphine, M3G and M6G concentrations were measured by reversed phase high performance liquid chromatography (Svensson et al, 1982;Svensson, 1986) with an intra-assay coefficient of variation of 5.9% at a morphine concentration of 5 nmol 1-1 and 4% at an M3G concentration of 100 nmol I-1. The limit of detection was 1 nmol -l 1for morphine and M6G and 10 nmol I-' for M3G.…”

Section: Analysesmentioning

confidence: 99%

The metabolism and bioavailability of morphine in patients with severe liver cirrhosis.

Hasselström

Eriksson

Persson

et al. 1990

Brit J Clinical Pharma

172

View full text Add to dashboard Cite

1. The oral and intravenous kinetics of morphine were investigated in seven cirrhotic patients with a history of encephalopathy. The plasma concentrations of morphine and its metabolites morphine‐3 (M3G) and morphine‐6 (M6G) were measured by h.p.l.c. 2. The mean terminal elimination half‐life of morphine was 4.2 h (95% CI 3.6‐4.8) the mean volume of distribution was 4.1 l kg‐1 (95% CI 2.9‐5.4) and the mean plasma clearance was 11.4 ml min‐1 kg‐1 (95% CI 8.1‐14.7). The mean oral bioavailability was 101% (95% CI 56‐147). 3. The plasma clearance of morphine was significantly lower, its terminal elimination half‐life longer and its oral bioavailability greater in the cirrhotic patients compared with patients with normal liver function. The metabolic ratio M3G/morphine was significantly lower in the cirrhotic patients than in control subjects after oral dosing, but did not differ after intravenous dosing. 4. The average urinary recoveries of morphine plus M3G and M6G were 49.9% after i.v. and 57.7% after oral administration. There were no statistically significant differences in the urinary recovery between the two routes of administration or between the cirrhotic patients and controls. 5. Specific changes in the EEG pattern could not be detected after intravenous dosage. 6. The metabolism of morphine is impaired significantly in patients with severe cirrhosis. Clinically important findings were a high oral bioavailability and a long elimination half‐life. These findings call for cautious dosing of oral and intravenous morphine in patients with severe end stage liver disease.

show abstract

Section: Analysesmentioning

confidence: 99%

The metabolism and bioavailability of morphine in patients with severe liver cirrhosis.

Hasselström

Eriksson

Persson

et al. 1990

Brit J Clinical Pharma

172

View full text Add to dashboard Cite

show abstract

“…Analytical methods M3G and morphine were measured by reversed phase ion-pair high performance liquid chromatography (Svensson et al, 1982), as previously reported . A new method, which is described below, had to be developed for the determination of M3S and M6S.…”

Section: Plan Ofstudymentioning

confidence: 99%

Morphine sulphation in children.

Choonara

Ekbom

Lindström

et al. 1990

Brit J Clinical Pharma

View full text Add to dashboard Cite

The metabolism of morphine was studied in nine children and seven preterm neonates receiving a continuous infusion of morphine. All the neonates and three children had detectable concentrations of morphine-3-sulphate (M3S) in urine. None of the neonates or the children had detectable concentrations of morphine-6-sulphate (M6S) in urine. None of the children had detectable concentrations of M3S in plasma. The M3S/morphine ratios were significantly higher in neonates than children (P < 0.01), suggesting that morphine sulphation decreases after the neonatal period. The amount of M3S formed, even in neonates, is low suggesting that this is a minor metabolic pathway.

show abstract

“…The metabolite concentrations were determined by reversed-phase ion pair high performance liquid chromatography according to Svensson et al (1982).…”

Section: Glucuronidation Assaymentioning

confidence: 99%

“…Morphine is increasingly used as a potent analgesic in cancer patients with severe chronic pain (Rane et al, 1982). In view of the escalated and extremely high doses that are often employed (Sawe et al, 1985) more knowledge about the mechanisms for its glucuronidation in the human liver is required.…”

Section: Introductionmentioning

confidence: 99%

Human liver morphine UDP‐glucuronyl transferase enantioselectivity and inhibition by opioid congeners and oxazepam

Wahlström

Pacifici

Lindström

et al. 1988

British J Pharmacology

Self Cite

View full text Add to dashboard Cite

1 Morphine uridine diphosphate glucuronyl transferase (UDP-GT) was studied in human liver microsomes. The (-)-and (+)-morphine enantiomers were used as substrates and inhibitors, such as oxazepam and various opioid congeners were employed to characterize the different glucuronidation pathways. The kinetics of the oxazepam inhibition were studied in the rat liver. 2 The overall glucuronidation of (+ )-morphine was higher than that of (-)-morphine. The morphine congeners tested, potently inhibited the formation of (-)-morphine-3-glucuronide ((-)-M3G), except for normorphine and codeine. The formation of ( + )-morphine-6-glucuronide ((+ )-M6G) was potently inhibited by only dextromethorphan and (+)naloxone. All drugs except normorphine inhibited the formation of(+)-M3G by 18-50%. 3 The metabolism of (-)-morphine to (-)-M3G was more sensitive to oxazepam inhibition than the formation of ( + )-M3G from (+ )-morphine in the rat liver. 4 The glucuronidation of natural morphine is subject to in vitro interaction with oxazepam and several opiate drugs. Our study supports the theory of more than one type of UDP-GT being involved in morphine glucuronidation.

show abstract

Determination of morphine, morphine-3-glucuronide and (tentatively) morphine-6-glucuronide in plasma and urine using ion-pair high-performance liquid chromatography

Cited by 269 publications

References 6 publications

The metabolism and bioavailability of morphine in patients with severe liver cirrhosis.

The metabolism and bioavailability of morphine in patients with severe liver cirrhosis.

Morphine sulphation in children.

Human liver morphine UDP‐glucuronyl transferase enantioselectivity and inhibition by opioid congeners and oxazepam

Contact Info

Product

Resources

About