ABSTRACT
Four hundred and fifty-four subjects with hyperamylasaemia were screened for the presence of macroamylase using polyethylene glycol precipitation (PEG) and the Beckman automated amylase assay based on the hydrolysis of maltotetraose. Twenty-five subjects (5.5%) exhibited PEG precipitation values suggestive of macroamylasaemia (MA) (>52% loss of original amylase activity). Macroamylasaemia was confirmed by gel filtration chromatography (GFC) in 21/25 subjects, using albumin as a molecular weight marker. Biochemical and clinical details of the 21 subjects identified are presented and discussed. It is recommended that serum exhibiting more than 57% precipitation of the original amylase activity by PEG should be examined by GFC to confirm or exclude MA.
Subject(s)
Amylases/blood , Amylases/chemistry , Chromatography, Gel , Clinical Enzyme Tests , Mass Screening/methods , Polyethylene Glycols , Chemical Precipitation , Humans , Hydrolysis , Immunoglobulin G/chemistry , Macromolecular Substances , Maltose/analogs & derivatives , Maltose/analysis , Maltose/chemistry , Metabolic Diseases/diagnosis , Metabolic Diseases/epidemiology , Oligosaccharides/analysis , Oligosaccharides/chemistry , Polyethylene Glycols/chemistry , Prevalence , United Kingdom/epidemiologyABSTRACT
Methylprednisolone-hemisuccinate (MPHS), methylprednisolone (MP), 20-alpha-hydroxy- (20 alpha HMP) and 20-beta-hydroxymethyl-prednisolone (20 beta HMP) concentrations were measured in serum, urine and bile from two liver transplant recipients who had received 1 g MPHS by a 1 h intravenous infusion for treatment of an acute rejection episode. These patients excreted similar total amounts of the dose in urine as patients with rheumatoid arthritis (historical controls) who had normal liver function. The transplant patients showed a ratio in urine of 'total metabolites'/MPHS that was one third that of patients with rheumatoid arthritis. Less than 0.2% of the administered MPHS appeared in bile as MPHS, MP, 20 alpha HMP and 20 beta HMP during the 24 h following infusion. Liver transplantation did not affect the overall elimination of drug in urine. However, the impaired liver function following transplantation resulted in reduced conversion of MPHS to its active form (MP).
Subject(s)
Graft Rejection/metabolism , Liver Transplantation/physiology , Methylprednisolone Hemisuccinate/metabolism , Adult , Bile/metabolism , Female , Graft Rejection/drug therapy , Humans , Liver Transplantation/immunology , Methylprednisolone Hemisuccinate/blood , Methylprednisolone Hemisuccinate/therapeutic use , Methylprednisolone Hemisuccinate/urine , Middle AgedABSTRACT
A reversed-phase high-performance liquid chromatographic (RP-HPLC) method for the measurement of methylprednisolone hemisuccinate (MPHS) and its metabolites methylprednisolone (MP), 20-alpha- (20a-HMP), and 20-beta-hydroxymethylprednisolone (20b-HMP) in urine is described. The metabolites were extracted from urine samples using Extrelut columns and eluted with ethylacetate. The mobile phase for RP-HPLC comprised methanol:citrate buffer:tetrahydrofuran (30:65:5, vol/vol/vol) with UV detection at 251 nm. Fractions were collected, pooled and the metabolites present were identified by gas chromatography-mass spectrometry and normal-phase HPLC (NP-HPLC). By RP-HPLC 30 +/- 7.3% (mean +/- 1 SD) of the dose was detected in the 0-24 h urine sample following a 1 g MPHS infusion to patients with rheumatoid arthritis; MPHS contributed 9.9 +/- 5.0%, MP 12.1 +/- 2.9%, 20a-HMP 7.8 +/- 2.2%, and 20b-HMP 1.0 +/- 0.3%, respectively. A further 1.0 +/- 0.9% of the administered dose was detected in urine collected 24-48 h postinfusion.
Subject(s)
Methylprednisolone Hemisuccinate/urine , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/urine , Chromatography, High Pressure Liquid , Gas Chromatography-Mass Spectrometry , Humans , Hydrolysis , Methylprednisolone/urine , Methylprednisolone Hemisuccinate/therapeutic use , Spectrophotometry, UltravioletABSTRACT
A rapid method for the measurement of methylprednisolone and its 21-hemisuccinate ester in plasma and urine following high dose pulse therapy is described. The drugs were extracted using Extrelut columns, eluted with ethyl acetate which was evaporated to dryness and the residue was reconstituted in chromatographic mobile phase. High-performance liquid chromatography was performed on a reversed-phase column using a mobile phase of acetonitrile-acetate buffer with detection at 251 nm. No interference from any drugs or endogenous compounds has been observed. The method has been used to analyse over 200 plasma and 150 urine samples from patients with rheumatoid disease or renal failure who have received high dose methylprednisolone hemisuccinate infusions.
Subject(s)
Methylprednisolone Hemisuccinate/blood , Methylprednisolone/analogs & derivatives , Methylprednisolone/blood , Acute Kidney Injury/blood , Acute Kidney Injury/drug therapy , Acute Kidney Injury/urine , Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/urine , Chromatography, High Pressure Liquid , Humans , Infusions, Parenteral , Kinetics , Methylprednisolone/therapeutic use , Methylprednisolone/urine , Methylprednisolone Hemisuccinate/urineABSTRACT
This article derives a number of equations which can be used in both continuous and the semicontinuous cultures of microorganism populations in chemostat systems. Using these equations, some phenomena which have been known for many years can be explained reasonably in terms of chemical kinetics, and a number of analytical solutions can be obtained instead of numerical solutions previously published.