Selective isolation procedures for GC/MS analysis of ethynyl steroids in biological material

Tetsuo, M.; Axelson, Magnus; Sjövall, Jan

doi:10.1016/0022-4731(80)90157-0

Cited by 24 publications

(5 citation statements)

References 43 publications

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“…Visiting professor David Collins performed elegant syntheses of 11ξ,12,12-trideutero-and 9α,11,11,12,12-pentadeuteroethinylestradiol (123,124), and methods for selective isolation of ethinyl steroids on a cation exchanger in silver form were developed (125)(126)(127). Unfortunately the project was not further supported, but labeled estradiols obtained as intermediates were used in studies of the turnover of estradiol in the rat uterus by H. Eriksson, M. Axelson, and postdoctoral student M. Tetsuo (128)(129)(130).…”

Section: Steroid Sulfates In Pregnancy and Intrahepatic Cholestasis Omentioning

confidence: 99%

Fifty years with bile acids and steroids in health and disease

Sjövall

2004

Lipids

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Cholesterol and its metabolites, e.g., steroid hormones and bile acids, constitute a class of compounds of great biological importance. Their chemistry, biochemistry, and regulation in the body have been intensely studied for more than two centuries. The author has studied aspects of the biochemistry and clinical chemistry of steroids and bile acids for more than 50 years, and this paper, which is an extended version of the Schroepfer Medal Award lecture, reviews and discusses part of this work. Development and application of analytical methods based on chromatography and mass spectrometry (MS) have been a central part of many projects, aiming at detailed characterization and quantification of metabolic profiles of steroids and bile acids under different conditions. In present terminology, much of the work may be termed steroidomics and cholanoidomics. Topics discussed are bile acids in human bile and feces, bile acid production, bacterial dehydroxylation of bile acids and steroids during the enterohepatic circulation, profiles of steroid sulfates in plasma of humans and other primates, development of neutral and ion-exchanging lipophilic derivatives of Sephadex for sample preparation and group separation of steroid and bile acid conjugates, profiles of steroids and bile acids in human urine under different conditions, hydroxylation of bile acids in liver disease, effects of alcohol-induced redox changes on steroid synthesis and metabolism, alcohol-induced changes of bile acid biosynthesis, compartmentation of bile acid synthesis studied with 3H-labeled ethanol, formation and metabolism of sulfated metabolites of progesterone in human pregnancy, abnormal patterns of these in patients with intrahepatic cholestasis of pregnancy corrected by ursodeoxycholic acid, inherited and acquired defects of bile acid biosynthesis and their treatment, conjugation of bile acids and steroids with N-acetylglucosamine, sulfate-glucuronide double conjugates of hydroxycholesterols, extrahepatic 7alpha-hydroxylation and 3-dehydrogenation of hydroxycholesterols, and extrahepatic formation of C27 bile acids. The final part discusses analysis of free and sulfated steroids in brain tissue by capillary liquid chromatography-electrospray MS and suggests a need for reevaluation of the function of steroid sulfates in rat brain.

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Section: Steroid Sulfates In Pregnancy and Intrahepatic Cholestasis Omentioning

confidence: 99%

Fifty years with bile acids and steroids in health and disease

Sjövall

2004

Lipids

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“…A mass spectrometric method for levonorgestrel was described by Tetsuo et al (1980). This method, like those for norethisterone, is very specific and can detect 5 pg/ml of levonorgestrel in plasma but it involves the use of sophisticated equipment.…”

Section: Levonorgestrelmentioning

confidence: 99%

Clinical Pharmacokinetics of Oral Contraceptive Steroids

Orme

Back

Breckenridge

1983

Clinical Pharmacokinetics

159

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Oral contraceptive steroids are of 2 types: oestrogens, of which ethinyloestradiol is the most important, and progestagens, of which levonorgestrel and norethisterone are the most commonly used. All these steroids can be measured by a number of analytical techniques but there is little doubt that radioimmunoassay is the most convenient. All. the steroids are well absorbed in humans but while levonorgestrel is completely bioavailable, norethisterone has an average bioavailability of 70%. Ethinyloestradiol, too, is subject to presystemic metabolism with a mean bioavailability of 40 to 45%. The main site of presystemic metabolism is the gut wall, with the production of ethinyloestradiol sulphate. The progestagens norethynodrel, ethynodiol diacetate and lynoestrenol are quantitatively metabolised to norethisterone.The pharmacokinetics of the contraceptive steroids are best described by a 2-compartment open model. The terminal plasma half-life of levonorgestrel varies from 11 to 45 hours and of norethisterone from 5 to 14 hours. The Ii-phase half-life of ethinyloestradiol varies from 6 to 20 hours. The apparent volume of distribution of these contraceptive steroids (after intravenous administration) is between 1.5 and 4.3 Llkg. During long term treatment with oral contraceptive steroids, steady-state plasma concentrations of ethinyloestradiol (24 hours after administration) are between 10 and 200 pg/m!. Plasma concentrations of norethisterone and levonorgestrel at steady-state are higher than predicted from the single-dose kinetics because of enhanced binding of the progestagens following the induction of sex hormone binding globulin (SHBG) by ethinyloestradiol. Concentrations are in the range of 1.6 to 15.2 nglml for norethisterone and 0.8 to 4.5 nglml for levonorgestrel.All the contraceptive steroids are bound to proteins in plasma. Ethinyloestradiol is 97 to 98% bound to plasma albumin. The progestagens are bound both to albumin (levonorgestrel 93 to 95%; norethisterone 79 to 80%) and more specifically to SHBG. The binding capacity of SHBG can be enhanced by treatment with ethinyloestradiol or with more conventional enzyme-inducing drugs such as phenobarbitone, carbamazepine or rifampicin.Norethisterone and levonorgestrel are chiefly metabolised by reduction in the A ring and this is followed by conjugation with glucuronide or sulphate. The metabolism of levonorgestrel is stereoselective. Ethinyloestradiol is primarily hydroxylated at the 2 position but a wide variety of hydroxylated and methylated metabolites are formed and these are present both free and as glucuronide and sulphate conjugates. Ethinyloestradiol is conjugated directly at the 3 position (unlike the progestagens) and thus is liable to enterohepatic recirculation. Ethinyloestradiol sulphate concentrations in plasma are many times higher than that of the unchanged drug.

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“…The cartridge was washed with 10 ml of water and steroids were then eluted with 10 ml of methanol [ 111. Distilled water and methanol was added to this eluate to give 20 ml of 72% (v/v) methanol which was filtered through SP-Sephadex C 25 (Pharmacia Fine Chemicals, Uppsala, Sweden) in H+-form [12]. The column was washed with 80 ml of 12% methanol and the combined eluates were neutralized to pH 7 with 0.1 mol/l aqueous sodium hydroxide, taken to dryness and redissolved in 20 ml of 72% ethanol.…”

Section: Analysis Of Bile Alcoholsmentioning

confidence: 99%

Urinary excretion of bile alcohols in normal children and patients with α₁‐antitrypsin deficiency during development of liver disease

Karlaganis

Németh

Hammarskjöld

et al. 1982

Eur J Clin Investigation

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Healthy infants and children were found to excrete bile alcohol glucuronides in urine. Following isolation and hydrolysis, the bile alcohols were estimated by capillary gas-liquid chromatography. The daily urinary excretion of the major compound, 27-nor-5 beta-cholestane-3 alpha, 7 alpha, 12 alpha, 24 xi, 25 xi-pentol (a C26 bile alcohol), ranged from 0.1 to 1.1 mumol/24 h per m2 body surface area for healthy infants and children. Two groups of patients with alpha 1-antitrypsin deficiency (phenotype PiZ) were also studied during infancy and childhood, and biochemical liver function tests and liver morphology were compared to the excretion of bile alcohols. The highest excretion of the C26 bile alcohol in urine was found in patients with alpha 1-antitrypsin deficiency and juvenile cirrhosis (2.1-8.4 mumol 24 h-1 m-2) regardless of preceding neonatal cholestasis. Patients with alpha 1-antitrypsin deficiency, neonatal cholestasis and subsequent fibrosis or normal liver morphology excreted bile alcohols within the normal range. The C26 bile alcohol constituted an average of 36% of the total bile alcohols in forty-three urine samples. This percentage was about the same in the three groups studied. The findings suggest that determination of urinary bile alcohols may be a valuable non-invasive diagnostic tool for patients with or at risk of developing liver cirrhosis.

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Selective isolation procedures for GC/MS analysis of ethynyl steroids in biological material

Cited by 24 publications

References 43 publications

Fifty years with bile acids and steroids in health and disease

Fifty years with bile acids and steroids in health and disease

Clinical Pharmacokinetics of Oral Contraceptive Steroids

Urinary excretion of bile alcohols in normal children and patients with α₁‐antitrypsin deficiency during development of liver disease

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Selective isolation procedures for GC/MS analysis of ethynyl steroids in biological material

Cited by 24 publications

References 43 publications

Fifty years with bile acids and steroids in health and disease

Fifty years with bile acids and steroids in health and disease

Clinical Pharmacokinetics of Oral Contraceptive Steroids

Urinary excretion of bile alcohols in normal children and patients with α1‐antitrypsin deficiency during development of liver disease

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Urinary excretion of bile alcohols in normal children and patients with α₁‐antitrypsin deficiency during development of liver disease