Paul J Taylor's research while affiliated with Princess Alexandra Hospital (Queensland Health) and other places

Publications (108)

Article
Background & Aims: Non-alcoholic fatty liver disease (NAFLD), characterized by accumulation of hepatic triglycerides (steatosis), is associated with abdominal obesity, insulin resistance, and inflammation. Although weight loss via calorie restriction reduces features of NAFLD, there is no pharmacologic therapy. Resveratrol is a polyphenol that prev...
Article
Full-text available
Context: Failure of aldosterone suppression by sodium loading during fludrocortisone suppression testing (FST) or saline suppression testing (SST) confirms primary aldosteronism (PA). We previously found recumbent SST (RSST) to lack sensitivity. Aldosterone levels can be higher upright (e.g. seated) than recumbent in patients with PA and upright l...
Article
Background: Melatonin is synthesized in the pineal gland and is an important circadian phase marker, especially in the determination of sleep patterns. Both temporary and permanent abnormal sleep patterns occur in children; therefore, it is desirable to have methods for monitoring melatonin in biological fluids in the diagnosis and treatment of su...
Article
Introduction: Accurate measurement of aldosterone and cortisol is crucial for diagnosis of primary aldosteronism (PA), but current assays lack specificity and precision. A semi-automated, simultaneous HPLC-tandem mass spectrometry (HPLC-MS/MS) method for aldosterone and cortisol was applied to fludrocortisone suppression testing (FST) and adrenal v...
Article
Serum hepcidin concentration is potentially affected by inflammation and iron stores in chronic liver disease (CLD), but little is known about the relationship between hepcidin and the degree of hepatic fibrosis. We investigated the potential role of serum hepcidin as a biomarker of advanced liver disease. Serum hepcidin was measured in 332 adults...
Article
Therapeutic drug monitoring (TDM) and more recently target concentration intervention (TCI) have been widely used in clinical practice for the optimization of drug treatment. TDM and TCI have been applied most frequently in the cardiovascular, respiratory, neurology, and infectious disease areas because the medications used here have both narrow th...
Article
Therapeutic drug monitoring of tacrolimus by high-performance liquid chromatography-tandem mass spectrometry has become standard practice. We report on the long-term (4.5 years) use of one such method. Whole blood samples (25 μL) were treated with zinc sulphate (100 μL) and acetonitrile containing ascomycin (internal standard, 250 μL). A high-perfo...
Article
Full-text available
A method for the simultaneous quantification of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) in human plasma by HPLC-tandem mass spectrometry (HPLC-MS/MS) was developed and validated. Free and esterified forms of fatty acids were hydrolysed from plasma samples in the presence of an internal standard and subjecte...
Article
The most popular screening test for primary aldosteronism is plasma aldosterone/renin ratio (ARR). Because both estrogen and progesterone affect aldosterone and renin levels, we studied effects of two contraceptives commonly used in our population, one oral and one subdermal, on ARR, measuring renin as both direct renin concentration (DRC) and plas...
Article
Plasma aldosterone to renin ratio (ARR) is the most popular screening test for primary aldosteronism (PAL). Certain medications are known to cause false-negative or -positive ARRs by affecting renin and aldosterone levels. There are no previously published data on the effects of antidepressants on ARR. Normotensive, depressed male patients (n = 26)...
Article
To examine the predictive performance of limited sampling methods for estimation of tacrolimus exposure in adult kidney transplant recipients. Twenty full tacrolimus area under the concentration-time curve from 0 to 12 h post-dose (AUC(0-12)) profiles (AUCf) were collected from 20 subjects. Predicted tacrolimus AUC(0-12) (AUCp) was calculated using...
Article
Therapeutic drug monitoring of critical dose immunosuppressant drugs is established clinical practice and there are similar good reasons to monitor antiretrovirals. The aim of this article is to review the recent literature (last five years), with particular reference to the use of liquid chromatography-tandem mass spectrometry (LC-MS/MS). LC-MS/MS...
Article
Multiple limited sampling strategies (LSSs) have been proposed for estimation of mycophenolic acid (MPA) area under the concentration-time curve from 0 to 12 hours postdose (AUC 0-12) after mycophenolate mofetil intake. The aim of this study was to provide summary information on all published LSSs for MPA and to evaluate their predictive performanc...
Article
Because primary aldosteronism is not uncommon, specifically treatable and in some cases curable, and carries higher risks for cardiovascular morbidity and mortality than essential hypertension, screening hypertensive patients for its presence by measuring aldosterone to renin ratio (ARR) is increasingly common. A significantly higher false-positive...
Article
Oxypurinol is the active metabolite of allopurinol which is used to treat hyperuricaemia associated with gout. Both oxypurinol and allopurinol inhibit xanthine oxidase which forms uric acid from xanthine and hypoxanthine. Plasma oxypurinol concentrations vary substantially between individuals and the source of this variability remains unclear. The...
Article
Mycophenolic acid is now the second most widely used immunosuppressant in solid organ transplantation. Overestimation of mycophenolic acid concentration is a recognized problem of immunoassay, and high-performance liquid chromatography with ultraviolet detection methods have long analysis times and a risk of analyte coelution which may compromise h...
Article
The most popular screening test for primary aldosteronism (PAL) is the plasma aldosterone to renin ratio (ARR). Medications, dietary sodium, posture, and time of day all affect renin and aldosterone levels and can result in false-negative or -positive ARR if not controlled. Opinions are divided on whether beta-adrenoreceptor blockers significantly...
Article
Availability and wider application of the plasma aldosterone/renin ratio (ARR) as a screening test for primary aldosteronism (PA) has led to the recognition that PA is the most common potentially curable and specifically treatable form of hypertension, possibly accounting for as many as 5-13% of patients. Aldosterone excess also has adverse cardiov...
Article
Full-text available
A multi-center evaluation (3 sites) of the LC/MS/MS MassTrak tacrolimus Immunosuppressants Kit (Kit) was undertaken. Ten aspects of the analytical performance of the Kit were investigated based on FDA and CLSI guidelines. The linear analytical range of the procedure was between 0.68 and 31.7ng/mL. Within-run and total imprecision were <6% and <8% (...
Article
Aldosterone and cortisol are useful biomarkers of dehydration and stress, respectively. The aim of this study was to develop an HPLC-tandem mass spectrometric method for the simultaneous measurement of aldosterone and cortisol in human plasma that could be applied to the study of athletes undergoing exercise and rehydration. Samples were prepared a...
Article
Reliable measurement of aldosterone with less interlaboratory variation than RIA would help standardize testing for primary aldosteronism. We set out to validate a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for aldosterone in human plasma. We prepared samples (EDTA plasma, lithium heparin plasma, and serum f...
Article
Simultaneous determination of the organophosphorus pesticides dimethoate, fenthion, diazinon and chlorpyrifos in human blood by HPLC-tandem mass spectrometry was developed and validated. The pesticides were extracted by a simple one-step protein precipitation procedure. Chromatography was performed on a Luna C(18) (30mmx2.0mm, 3microm) column, usin...
Poster
Introduction There is an urgent need to develop a highly reliable method of measuring aldosterone to aid detection of endocrine forms of hypertension such as primary aldosteronism. This study sought to clinically validate an LC/MS/MS approach to aldosterone measurement in human plasma. Methods Samples (EDTA and Li+ heparin plasma, and serum from se...
Poster
Full-text available
Introduction LC/MS/MS is becoming the method of choice for some routine clinical applications, particularly for therapeutic drug monitoring (TDM). However, these “home-brew” LC/MS/MS assays require extensive development and validation before they can be used routinely and they are not standardised between laboratories. These factors create an adopt...
Article
Concentration monitoring and dose individualization is required to optimize either tacrolimus or cyclosporin therapy. In this study, the validation of a simple, rapid high-performance liquid chromatography-tandem mass spectrometry method for the simultaneous measurement of tacrolimus and cyclosporin in whole blood is reported. Blood samples (100 mi...
Article
The immunosuppressant drug tacrolimus has a narrow therapeutic index and is subject to a large variation in individual bioavailability and clearance. With its narrow therapeutic index, therapeutic drug monitoring is standard clinical practice in the management of transplant recipients. In this study, we report the evaluation of the cloned enzyme do...
Article
To investigate if the feeding of silibinin (an anticancer flavonoid) to mice inhibits in vivo renal cell carcinoma (RCC) growth via changes in insulin-like growth factor binding protein-3 (IGFBP-3) levels. Male severe combined immunodeficiency disease (SCID) mice (7 weeks old), with left kidneys injected with 1 million SN12K1 cells, were fed a sili...
Article
Serotonin is a major neurotransmitter that controls many functions, ranging from mood and behaviour through to sleep and motor functions. The non-enzymatic oxidation of serotonin is of significant importance as some oxidation products are considered to be neurotoxic. An interaction between copper and serotonin has been suggested by symptoms observe...
Article
We report here the validation of an HPLC-electrospray-tandem mass spectrometry method for the quantification of everolimus, an immunosuppressant drug. Whole blood samples (100 microl) were extracted by protein precipitation which involved sample pre-treatment with zinc sulphate followed by acetonitrile (containing internal standard, 40-O-(3'-hydrox...
Article
Numerous in vitro studies suggest that sphingosine 1-phosphate (S1P), a bioactive lysosphingolipid associated with high-density lipoproteins, accounts at least partly for the potent antiinflammatory properties of high-density lipoprotein and, thereby, contributes to the antiatherogenic potential attributed to high-density lipoproteins. The present...
Article
Full-text available
Introduction: The use of HPLC with tandem mass spectrometric (MS/MS) detection is becoming increasingly common in clinical laboratories particularly for the monitoring of immunosuppressant drugs such as tacrolimus. The sensitivity and selectivity of HPLC/MS/MS allow accurate and precise quantification of parent drug in the presence of metabolites a...
Article
We report here a validated method for the quantification of a new immunosuppressant drug FTY720, using HPLC-tandem mass spectrometry. Whole blood samples (500 microl) were subjected to liquid-liquid extraction, in the presence of an internal standard (Y-32919). Mass spectrometric detection was by selected reaction monitoring with an atmospheric pre...
Article
Mycophenolic acid (MPA) is a drug that has found widespread use as an immunosuppressive agent which limits rejection of transplanted organs. Optimal use of this drug is hampered by gastrointestinal side effects which can range in severity. One mechanism by which MPA causes gastropathy may involve a direct interaction between the drug and gastric ph...
Article
This study compared the performance of a fluorescent polarization immunoassay (FPIA) against HPLC-tandem mass spectrometry (HPLC-MS) for the measurement of everolimus in renal transplant recipients. A total of 333 pre-dose samples from 45 renal transplant patients were analyzed by FPIA and HPLC-MS. The inter-batch inaccuracy and precision of the FP...
Article
Therapeutic monitoring with dosage individualization of sirolimus drug therapy is standard clinical practice for organ transplant recipients. For several years sirolimus monitoring has been restricted as a result of lack of an immunoassay. The recent reintroduction of the microparticle enzyme immunoassay (MEIA) for sirolimus on the IMx analyser has...
Article
The development of HPLC-atmospheric pressure ionization-mass spectrometry (HPLC-MS) has presented clinical laboratories with a powerful analytic tool. The aim of this paper is to provide an overview of the current status of HPLC-MS in the clinical laboratory; to discuss the challenges to mass spectrometry in this setting; and to present some of the...
Article
Full-text available
The calcineurin inhibitor cyclosporin A (CsA) is used as a primary immunosuppressant in solid organ transplantation and for the treatment of many autoimmune diseases. Individualization of therapy is required because CsA has high inter- and intrapatient pharmacokinetic variability, the potential for drug interactions, a narrow therapeutic index, and...
Article
Cyclosporin is an immunosuppressant drug with a narrow therapeutic window. Trough and 2-h post-dose blood samples are currently used for therapeutic drug monitoring in solid organ transplant recipients. The aim of the current study was to develop a rapid HPLC-tandem mass spectrometry (HPLC-MS) method for the measurement of cyclosporin in whole bloo...
Article
The role of the therapeutic drug monitoring laboratory in support of immunosuppressant drug therapy is well established, and the introduction of sirolimus (SRL) is a new direction in this field. The lack of an immunoassay for several years has restricted the availability of SRL assay services. The recent availability of a CEDIA SRL assay has the po...
Article
High-performance liquid chromatography coupled by an electrospray ion source to a tandem mass spectrometer (HPLC-ESI-MS/MS) is the current analytical method of choice for quantitation of analytes in biological matrices. With HPLC-ESI-MS/MS having the characteristics of high selectivity, sensitivity, and throughput, this technology is being increasi...
Article
The pharmacokinetics of mycophenolic acid and its glucuronide are complex. This study investigated the pharmacokinetics, pharmacodynamics and protein binding of mycophenolic acid and its glucuronide metabolite, early post-transplant in renal allograft recipients. Forty-two de novo renal transplant recipients receiving mycophenolate mofetil and conc...
Article
The aim of this study was to determine the most informative sampling time(s) providing a precise prediction of tacrolimus area under the concentration-time curve (AUC). Fifty-four concentration-time profiles of tacrolimus from 31 adult liver transplant recipients were analyzed. Each profile contained 5 tacrolimus whole-blood concentrations (predose...
Article
The authors describe a reverse-phase high-performance liquid chromatography-electrospray-tandem mass spectrometry method for the measurement of nicotine in human plasma. Samples (500 microL) with added deuterium-labeled d3-nicotine as an internal standard (IS) were treated with a 2-step process of ether extraction (6 mL) followed by back-extraction...
Article
A 58-year-old man with end-stage renal failure secondary to polycystic kidney disease developed a profoundly elevated mycophenolic acid (MPA) free fraction and associated severe toxicity after cadaveric renal transplantation. Initial immunosuppressive therapy was 4 mg/kg body weight bid cyclosporin (Neoral; Novartis Pharmaceutical Co Ltd, Sydney, A...
Article
The current approach for therapeutic drug monitoring in renal transplant recipients receiving mycophenolate mofetil (MMF) is measurement of total mycophenolic acid (MPA) concentration. Because MPA is highly bound, during hypoalbuminemia the total concentration no longer reflects the free (pharmacologically active) concentration. The authors investi...
Article
The currently expanding range of immunosuppressant agents has placed new challenges on therapeutic drug-monitoring (TDM) services. Many of these drugs require the measurement of concentrations with subsequent dosage adjustment to maximize efficacy while minimizing toxicity. HPLC-mass spectrometry (HPLC-MS) is a relatively new technique for drug qua...
Article
Although monitoring of tacrolimus blood concentrations is standard clinical practice following liver transplantation, a greater understanding of the relationship between trough concentrations and clinical outcome is required. The aim of this study was to perform a pharmacodynamic investigation of tacrolimus in pediatric liver transplant recipients....
Article
The development of hyperlipidemia after liver transplant is frequently treated with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) such as atorvastatin. As atorvastatin and the primary immunosuppressant drug, cyclosporine, are metabolized by the same pathway, there is the potential for an interaction. To determine the effect of ato...
Article
Oral iron supplements are frequently prescribed to renal transplant recipients in the early posttransplant period. A recent trial in seven healthy volunteers demonstrated a significant 91% reduction in mycophenolate mofetil (MMF) absorption when coadministered with oral iron. However, the effect of iron on MMF absorption in renal transplant patient...
Article
The immunosuppressant drug mycophenolic acid (MPA) and its major metabolite, mycophenolic acid glucuronide (MPAG), are highly bound to albumin. An HPLC-tandem-MS (HPLC/MS/MS) and an HPLC-UV assay were developed to measure free (unbound) concentrations of MPA and MPAG, respectively. Ultrafiltrate was prepared from plasma (500 microl) by ultrafiltrat...
Article
Free drug measurement and pharmacodymanic markers provide the opportunity for a better understanding of drug efficacy and toxicity. High-performance liquid chromatography (HPLC)–mass spectrometry (MS) is a powerful analytical technique that could facilitate the measurement of free drug and these markers. Currently, there are very few published meth...
Article
Patient outcomes in transplantation would improve if dosing of immunosuppressive agents was individualized. The aim of this study is to develop a population pharmacokinetic model of tacrolimus in adult liver transplant recipients and test this model in individualizing therapy. Population analysis was performed on data from 68 patients. Estimates we...
Article
The aims of this study were to investigate the population pharmacokinetics of tacrolimus in adult kidney transplant recipients and to identify factors that explain variability. Population analysis was performed on retrospective data from 70 patients who received oral tacrolimus twice daily. Morning blood trough concentrations were measured by liqui...
Article
This study compared an enzyme-linked immunosorbent assay (ELISA) to a liquid chromatography-tandem mass spectrometry (LC/MS/MS) technique for measurement of tacrolimus concentrations in adult kidney and liver transplant recipients, and investigated how assay choice influenced pharmacokinetic parameter estimates and drug dosage decisions. Tacrolimus...
Article
We report here a validated method for the quantification of a new immunosuppressant drug, everolimus (SDZ RAD), using HPLC-tandem mass spectrometry. Whole blood samples (500 microl) were prepared by protein precipitation, followed by C(18) solid-phase extraction. Mass spectrometric detection was by selected reaction monitoring with an electrospray...
Article
Full-text available
We report the validation of a quantitative method for paraquat in plasma and urine using high-performance liquid chromatography (HPLC) with ultraviolet detection (260 nm). Furthermore, we illustrate the use of this method in the clinic (over five years), in conjunction with a qualitative urine paraquat screen. Urine or plasma sample (1 mL) preparat...