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PubMedDate not supplied

Potential utility of rubidium 82 PET quantification in patients with 3-vessel coronary artery disease.

BACKGROUND: Standard perfusion imaging may underestimate the extent of disease in 3-vessel coronary atherosclerosis. This study determined whether positron emission tomography quantification of perfusion reserve by use of rubidium 82 net retention defined a greater extent of disease than the standard approach in patients with 3-vessel disease. METHODS AND RESULTS: Rb-82 net retention was quantified as an estimation of absolute perfusion at rest and with dipyridamole stress by use of dynamic positron emission tomography imaging. The percent of abnormal myocardial sectors, as compared with a normal database, for a standard and quantification approach was determined. Twenty-three patients were evaluated. Defect sizes were larger in patients with 3-vessel disease (n = 13) by use of quantification methods: 44% +/- 18% of the myocardial sectors were abnormal by use of the standard approach versus 69% +/- 24% of sectors when measured by quantification of the stress-rest perfusion difference (P =.008). In patients with single-vessel disease (n = 10), defect sizes were smaller with quantification methods. CONCLUSIONS: Quantification of Rb-82 net retention to measure the stress-rest perfusion difference in the myocardium defined a greater extent of disease than the standard approach in this group of patients with triple-vessel disease. More accurate measurement of the extent of coronary artery disease could facilitate better risk stratification and identify more high-risk patients in whom aggressive intervention is required.

Aged↗

PubMed1996

Pharmacokinetics and absolute bioavailability of epristeride in healthy male subjects.

The objective of the current investigation was to describe the pharmacokinetics and absolute oral bioavailability of epristeride. Twelve healthy male subjects (mean (SD) age, 27 (6.2) years) received a single oral dose of 5 mg and an intravenous infusion of 4.5 mg over 30 min in a crossover fashion. Blood samples were obtained over 72h for the determination of epristeride plasma concentrations using a sensitive high-performance liquid chromatography assay. The lower limit of quantification was 5 ng mL-1. Pharmacokinetic analysis of the plasma concentration-time data was performed by both non-compartmental and compartmental methods. Absolute bioavailability was determined using dose-normalized AUC values following oral and intravenous administration. Epristeride plasma concentrations declined in a biexponential fashion with secondary peaks evident around 24 h in a majority of subjects following both routes of administration. Maximal plasma concentrations were typically achieved approximately 4 h after oral dosing. The mean apparent terminal elimination half-life estimates were similar following intravenous and oral administration and were 27.3 and 26.2 h, respectively. The mean plasma clearance and steady-state volume of distribution were 0.33 (0.09) mL min-1 kg-1 and 0.54 (0.17) L kg-1, respectively. The mean absolute bioavailability was 93% (95% CI: 84%, 104%). Following compartmental analysis of the intravenous data, the mean (SD) lambda 1 and lambda 2 half-life estimates were 2.74 (0.48) and 31.8 (19.5) h, respectively. The % AUC associated with the lambda 2 exponential phase was approximately 68%. This long half-life allows for once-daily dosing of epristeride.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2000

Comparison of different derivatization approaches for mercury speciation in biological tissues by gas chromatography/inductively coupled plasma mass spectrometry.

A novel interface design for coupling gas chromatography and inductively coupled plasma mass spectrometry (GC/ICP-MS) was used to perform mercury speciation in biological tissues. Three derivatization approaches were optimized and compared for this purpose: anhydrous butylation using a Grignard reagent, aqueous ethylation by means of NaEt(4)B and aqueous propylation with NaPr(4)B. The last reagent was synthesized in the laboratory as it is not commercially available. Detection limits obtained by GC/ICP-MS ranged between 100 and 200 fg (as absolute mass) for methylmercury and between 500 and 600 fg for inorganic mercury using a 1 microl injection. Quantification of methyl- and inorganic mercury was carried out by resorting to aqueous calibration, using ethylmercury as internal standard for both propylation and butylation derivatization techniques. For ethylation procedures, a methylpropylmercury solution was used as internal standard. The absence of transmethylation during sample preparation was checked using a 97% enriched (202)Hg inorganic standard. The accuracy of the three derivatization approaches was evaluated by the analysis of the certified reference material DOLT-2 (dogfish liver) from the National Research Council of Canada and certified for methylmercury, with satisfactory results.

Animals↗

PubMed2002

Using three-dimensional difference maps to assess changes in scoliotic deformities.

The three-dimensional nature of scoliosis, coupled with changes due to natural history or treatment, is often difficult to quantify and visualise. A difference map was developed to compare the sequential surface topography of subjects over their treatment period. Three-dimensional surface maps representing patients' trunk surfaces were captured with a laser scanner. Patient surface maps from two clinic visits were matched using a manual best-fit technique that accounted for growth and positioning. The surfaces were subtracted, generating a colour-coded three-dimensional difference map displaying the surface changes. The difference maps were compared with known clinical measures, indicating good agreement (78% specific) with the clinical parameters in detecting change. Full agreement or agreement with the clinical parameters occurred in the surgical, brace and no treatment groups: 76%, 80% and 85%, respectively. A difference index (average of the absolute value of differences on a point-by-point basis) was calculated from the difference map, enabling quantification of change. The difference index, with zero being a perfect match, averaged 5 +/- 1 for repeated measures 7 +/- 2 for subjects deemed to have no change, 9 +/- 2 for subjects with slight change, and 14 +/- 2 for subjects with significant change. The difference map showed the extent and location of changes and is a useful tool for assessing surface topography changes.

Adolescent↗

PubMed2006

Electrospray ionization LC-MS/MS validated method to quantify griseofulvin in human plasma and its application to bioequivalence study.

A simple, sensitive and rapid liquid chromatography/tandem mass spectrometry (LC-MS/MS) method has been developed and validated to quantify griseofulvin in human plasma using propranolol hydrochloride as internal standard (IS). Samples were prepared using solid phase extraction and analysed without drying and reconstitution. The analytes were chromatographed on Hypersil, hypurity C18 reverse phase column under isocratic conditions using 0.05% formic acid in water:acetonitrile (30:70, v/v) as the mobile phase. Total chromatographic run time was 3.0 min. Quantitation was done on a triple quadrupole mass analyzer API-3000, equipped with turbo ion spray interface and operating in multiple reaction monitoring (MRM) mode to detect parent-->product ion transition for analyte and IS. The method was validated for sensitivity, matrix effect, accuracy and precision, linearity, recovery and stability studies. Linearity in plasma was observed over the concentration range 20-3000 ng/mL for griseofulvin. Lower limit of quantification (LLOQ) achieved was 20 ng/mL with precision (CV) less than 10% using 5 microL injection volume. The absolute recovery of analyte (87.36%) and IS (98.91%) from spiked plasma samples was consistent and reproducible. Inter-batch and intra-batch coefficients of variation across four validation runs (LLOQ, LQC, MQC and HQC) was less than 7.5%. The accuracy determined at these levels was within +/-4.2% in terms of relative error. The method was applied to a pilot bioequivalence study of 500 mg griseofulvin tablet in six healthy human subjects under fed condition.

Antifungal Agents↗

PubMed1997

Quantitation of messenger RNA by competitive RT-PCR: a simplified read out assay.

A competitive RT-PCR method that permits reliable quantification of minute amounts of reverse-transcribed mouse lymph node mRNA is described. Using this technique, an absolute number of cDNA copies ranging from 10(3) to 10(5) can be determined, with a precision superior to 25%. The standard templates described in the present study permit the quantitation of beta-actin, IFN gamma, IL2, IL3, IL4, IL10, IL12 (p40 subunit), TGF beta 1, inducible nitric oxide synthase, ELAM-1, VCAM-1, and ICAM-1 mouse mRNA. The expression of a particular transcript is normalized to an arbitrary number of actin transcripts. The standard templates and wild-type cDNA have nearly identical sequences, but they can be distinguished by unique restriction sites. Known amounts of these standard templates, are co-amplified with serial dilutions of the cDNA derived from the mRNA of interest. Oligonucleotide primer pairs possessing 3' octamers found infrequently in the mouse genome (< or = 0.26 x 10(-6)) are used to amplify sequences, chosen to contain no GC stretches longer than 8 (PCRare software) (Griffais et al., 1991). Samples of each PCR product are digested separately with restriction endonucleases unique either for the wild-type or the standard amplicon. The quantitation of the test product and the standard product is easily carried out following their electrophoresis in an ethidium bromide-stained agarose gel.

Actins↗

PubMed1999

Quantitative determination of cefepime in plasma and vitreous fluid by high-performance liquid chromatography.

An isocratic reversed-phase HPLC method was developed to determine cefepime levels in plasma and vitreous fluid. Cefepime and the internal standard cefadroxil were separated on a Shandon Hypersil BDS C18 column by using a mobile phase of 25 mM sodium dihydrogen phosphate monohydrate (pH 3) and methanol (87:13, v/v). Ultraviolet detection was carried out at 270 nm. The retention times were 4.80 min for cefepime and 7.70 min for cefadroxil. This fast procedure which involves an efficient protein precipitation step (addition of HClO4), allows a quantification limit of 2.52 microg ml(-1) and a detection limit of 0.83 microg ml(-1). Recoveries and absolute recoveries of cefepime from plasma were 96.13-99.44% and 94-102.5% respectively. The intra-day and inter-day reproducibilities were less than 2% for cefepime at 10, 30, 50 microg ml(-1) (n=10). The method was proved to be suitable for determining cefepime levels in human plasma and was modified to measure vitreous fluid samples.

Aged↗

PubMed1997

Functional characteristics of myocardial bridging. A combined angiographic and intracoronary Doppler flow study.

AIMS: Combined quantitative coronary angiography and intracoronary Doppler flow velocity measurements were performed to study the underlying haemodynamic mechanisms leading to myocardial ischaemia in patients with myocardial bridging in the absence of coronary artery disease. METHODS AND RESULTS: In 42 symptomatic patients with myocardial bridging of the left anterior descending coronary artery, quantitative coronary angiography was used to measure absolute and relative vessel diameters during systole and diastole. In 14 patients, serial frame-by-frame diameter quantification during a complete cardiac cycle was performed. Intracoronary blood flow velocities were determined using a 0.014 inch Doppler flow guide wire proximal, within, and distal to myocardial bridges, and coronary flow reserve was calculated. Quantitative coronary angiography revealed a maximal systolic lumen diameter reduction of 71 +/- 16% with a persistent diameter reduction of 35 +/- 13% during mid-diastole. Flow velocities revealed increased average diastolic peak flow velocities within myocardial bridges of 38.6 +/- 19 cm.s-1 vs 22.4 +/- 7.7 cm.s-1 proximal and 18.6 +/- 4.6 cm.s-1 distal (P < 0.001), which increased during rapid pacing (64.7 +/- 25 cm.s-1, P < 0.001 vs baseline). Coronary flow reserve distal to myocardial bridges was 2.3 +/- 0.9 (vs 2.9 +/- 0.9 proximal, P < 0.05). There was a characteristic Doppler flow profile within myocardial bridges with an early diastolic overshoot, which was further augmented during rapid pacing. CONCLUSION: Myocardial bridging is characterized by a delay in diastolic lumen gain and a concomitant increase in diastolic intracoronary Doppler flow velocities, which are enhanced by rapid pacing. In combination with a reduced coronary flow reserve and anginal symptoms these findings support the concept of a haemodynamically significant obstruction to coronary flow due to myocardial bridging in a selected subset of patients.

Blood Flow Velocity↗

PubMedDate not supplied

Effect of hearing loss, centre frequency, and bandwidth on the shape of loudness functions in categorical loudness scaling.

Loudness functions of narrow-band and broad-band stimuli were measured with eight normally-hearing and eight hearing-impaired listeners using a categorical loudness scaling method. In the normally-hearing listeners, narrow-band stimuli, generally generated loudness functions whose slope increased with increasing level, whereas broad-band stimuli generated more linear loudness functions. These differences can be explained by the level dependence of spectral loudness summation, which is known to be most prominent at moderate levels. In the hearing-impaired listeners, the narrow-band loudness functions generally showed a more linear shape than in the normally-hearing listeners. A consequence of these findings might be that the optimal shape of the input/output curve of a hearing aid is affected not only by the signal power in the respective frequency channels but also by the bandwidth of the input signal. However, there were considerable differences between listeners in both groups regarding the individual shape and absolute position of the loudness functions. Therefore, no normative reference could be extracted that would allow for a quantification of the bandwidth effect on an individual basis.

Adult↗

PubMed2003

Automated selection of DAB-labeled tissue for immunohistochemical quantification.

The increased use of immunohistochemistry (IHC) in both clinical and basic research settings has led to the development of techniques for acquiring quantitative information from immunostains. Staining correlates with absolute protein levels and has been investigated as a clinical tool for patient diagnosis and prognosis. For these reasons, automated imaging methods have been developed in an attempt to standardize IHC analysis. We propose a novel imaging technique in which brightfield images of diaminobenzidene (DAB)-labeled antigens are converted to normalized blue images, allowing automated identification of positively stained tissue. A statistical analysis compared our method with seven previously published imaging techniques by measuring each one's agreement with manual analysis by two observers. Eighteen DAB-stained images showing a range of protein levels were used. Accuracy was assessed by calculating the percentage of pixels misclassified using each technique compared with a manual standard. Bland-Altman analysis was then used to show the extent to which misclassification affected staining quantification. Many of the techniques were inconsistent in classifying DAB staining due to background interference, but our method was statistically the most accurate and consistent across all staining levels.

Animals↗

PubMed1988

A quantitative method for evaluating the effects of drugs on bone marrow cellularity using the same experimental animal. Quantification of the effects of a single dose of busulphan.

A method for quantifying the cellularity of rats bone marrow per unit of weight is described. Absolute numbers of each cell type per mg of bone marrow in the left and right femurs of the same experimental animal were determined at different times. In normal rats in which both femurs were studied simultaneously it was found that the absolute counts of each cell type per mg of bone marrow in the left and right femurs did not differ, nor were differences found in absolute numbers of marrow cells when the quantitative analyses from the left femurs were compared with those of the right femurs of the same animal, 10 and 20 days later. In order to test the validity of the present method for evaluating the effects of drugs on hematopoiesis, a single oral dose of busulphan (20 mg/kg), was administered to normal rats immediately after the marrow quantitative studies of the left femurs were performed. A marked and significant reduction in total nucleated cell was seen in marrows from the right femurs, 10 days later. Cellular effects were particularly pronounced on the myeloid line. Results presented here indicate that the quantitative study employed is a simple and useful method to evaluate the effects of drugs on hematopoiesis. The novelty of this method lies in: 1) its expression of cellularity on a per mg marrow basis, thereby avoiding possible misinterpretations of data which occur when results are expressed as percentages and 2) the analysis of contralateral femoral marrow specimens obtained from the same animal before and after drugs treatment. Therefore, each animal acts as its own control avoiding possible errors in the determination of drug-induced hematopoietic changes due to inter-animal variability.

Animals↗

PubMedDate not supplied

[Gel agglutination test--a new test system for semiquantitative detection of feto-maternal transfusion in Rhesus incompatibility].

BACKGROUND: The postpartum administration of an adequate amount of anti-D immunoglobulin to the mother in cases of Rhesus incompatibility requires the exact quantification of the amount of Rh-positive fetal cells that may be present in the Rh-negative maternal circulation. The classical methods to detect an intrapartum fetomaternal hemorrhage are either time-intensive (such as the Kleihauer-Betke test), of low specificity (such as the indirect Coombs test), or technically cumbersome (such as flow cytometry). The goals of our study were to develop a simple screening test that may be used routinely to quantify fetomaternal hemorrhage in cases of Rhesus incompatability and to evaluate this test in clinical practice. STUDY DESIGN AND METHODS: In cases of Rhesus-negative mothers of Rhesus-positive neonates, 2.5 ml of maternal Rhesus negative blood was sampled in an EDTA tubes immediately postpartum and was incubated with anti-D antibodies. Thereafter, a semiquantitative determination was made of the amount of antibody that remained unbound in the serum via a gel agglutination test (GAT) (DiaMed., Switzerland) after mixing with test red blood cells. The amount of anti-D consumed (bound to fetal cells in the first phase) is the semi-quantitatively indicated by the degree of positivity in the second phase the weaker reaction--the more anti-D absorbed in the first phase--the more Rhesus-positive fetal cells present in the maternal sample--the larger the fetomaternal hemorrhage. Following the development of a discrimination zone using this GAT which could ascertain an Rhesus-positive erythrocyte concentration of over 0.2%, the test was applied in a clinical setting. Between September 1995 and April 1998 in unselected postpartum blood samples from 603 Rhesus negative parturients, the GAT was used to test the same blood samples as those requiring evaluation for HbF concentration using the traditional Kleihauer-Betke test. RESULTS: In 585 of the 603 cases (97%) there was no evidence of a fetomaternal transfusion following testing using both methods. Furthermore, both tests showed significant evidence for a fetomaternal transfusion in five cases. The Kleihauer-Betke test was false-positive in three cases of mothers who had a hereditary elevation of the HbF concentration. The GAT showed three false-positive reaction due to a Dweak maternal varient. In two cases, the disparity between the GAT and the Kleihauer-Betke test could be attributed to an antecedant dose of anti-D antibody. In the two cases, the Kleihauer-Betke test results were 0.3% while the GAT was only 0.2%. CONCLUSION: The GAT may be used as a screening method in routine clinical practice. This is a quick test that allows for the specific determination and semiquantitative evaluation of the Rh-positive erythrocyte concentration in clinically relevant concentrations. Thus, following a positive GAT screening test, a further specific test such as the Kleihauer-Betke test may be utilized to absolutely quantify the amount of blood transfused from fetus to mother. It is also possible to perform such a quantification test with the GAT by eventually using a diluted maternal blood sample.

Female↗

PubMed2004

Simultaneous quantification of human cardiac alpha- and beta-myosin heavy chain proteins by MALDI-TOF mass spectrometry.

We have developed a novel method for quantifying protein isoforms, in both relative and absolute terms, based on MALDI-TOF mass spectrometry. The utility of the approach is demonstrated by quantifying the alpha and beta protein isoforms of myosin heavy chain (MyHC) in human atrial tissue. Alpha-MyHC (726-741) and beta-MyHC (724-739) were identified as isoform-specific tryptic peptides. A calibration curve was constructed by plotting ion current ratios against molar ratios of the two peptides prepared synthetically. MyHC was digested by trypsin and the ion current ratio determined for the two tryptic peptides. The ion current ratio was converted to the peptide ratio and hence the isoform ratio by reference to the standard curve. The accuracy of the method was confirmed by a comparison between these results and those determined by an established method of MyHC isoform ratio determination. So that the molar ratio could be converted to absolute values, a third peptide, an analogue of the two peptides being measured, was synthesized for use as an internal standard (IS). The measured ion current ratios of synthetic alpha-MyHC (726-741), beta-MyHC (724-739), and IS peptides were used to generate standard curves. A known quantity of the IS was added to the MyHC digests. The measured ion current ratios were converted to the actual quantities of the isoform-specific peptides and hence the actual quantity of each protein isoform by reference to the standard curves. This method is of general applicability, especially when isoform quantification is required.

Humans↗

PubMed1993

Volumetric arterial flow quantification using echo contrast. An in vitro comparison of three ultrasonic intensity methods: radio frequency, video and Doppler.

The two hypotheses presented in this paper are: (1) absolute and relative volumetric flow rates in vessels can be measured by echo contrast time-intensity curves; and (2) echo contrast time-intensity curves generated by different ultrasound backscatter intensity techniques have equivalent capability for flow measurements. A nonpulsatile flow system was built for quantitative ultrasound backscatter measurements from bolus echo contrast injections using two different volumes of mixing. A total of 49 echo contrast bolus injections were made at various flow rates (0.44-2.59 L/min). Ultrasound backscatter time-intensity curves were generated by ultrasound radio frequency, video and Doppler techniques. The rate of backscattered ultrasound intensity washout for each technique (WASHOUT RATE), and relative change in WASHOUT RATE (delta WASHOUT RATE) were compared to the volumetric flow rate (FLOW) and changes in flow rate (delta FLOW), respectively. The relationship between WASHOUT RATE, FLOW and the volume of contrast mixing was studied. A linear relationship was demonstrated between WASHOUT RATE and delta WASHOUT RATE and the corresponding FLOW and delta FLOW by all three methods (r > 0.90 for all comparisons). The WASHOUT RATE was found to depend on the FLOW and the volume of contrast mixing, but the delta WASHOUT RATE was equal to the delta FLOW and independent of the volume of mixing. Time-intensity curves can be generated from different ultrasound backscatter intensity techniques and the WASHOUT RATE correlates well with FLOW. delta FLOW can be determined directly from the corresponding delta WASHOUT RATE. Doppler ultrasound, because of its natural association with the assessment of flow in chambers and vessels, is uniquely suited to assessment of arterial volumetric blood flow in vitro.

Arteries↗

PubMed1989

Flow cytometric quantification of rat spermatogenic cells after hypophysectomy and gonadotropin treatment.

DNA flow cytometry was evaluated as a tool to analyze stage-specific changes that occur in absolute cell numbers in the testes. Hypophysectomy was selected as a model system for perturbing testicular cell types, since the cytological sequelae of this treatment post-hypophysectomy in the rat are well documented in the literature. Rat spermatogenic cells in stages II-V, VII, and IX-XIII of the seminiferous epithelial cycle (as defined by Leblond and Clermont, 1952) were quantified in numbers per standard length of seminiferous tubule by DNA flow cytometry after hypophysectomy and subsequent gonadotropin treatment. In agreement with previous histological studies, we found that acrosome- and maturation-phase spermatids disappeared from the seminiferous epithelium after 17 days post-hypophysectomy, whereas meiosis and early spermiogenesis continued at least 164 days. The number of meiotic cells and round spermatids gradually decreased after hypophysectomy. Changes were observed as early as Day 6 post-hypophysectomy. Treatment with human chorionic gonadotropin (hCG) alone maintained most cell numbers within normal limits, and follicle-stimulating hormone (FSH) was needed in addition to hCG to maintain the normal number of cells with the amount of DNA contained in primary spermatocytes and spermatogonia in G2/M-phase (4C) in stages IX-XIII and elongated spermatids (1C') in stages II-V of the epithelial cycle. The absolute numbers of spermatogenic cells at different phases of maturation provide a useful reference for quantitative studies of spermatogenesis. Pathological changes in the seminiferous epithelium can be detected and quantified by DNA flow cytometry.

Acrosome↗

PubMed2004

Age estimation from aspartic acid racemization of root dentin by internal standard method.

In this study, we investigated the application of the internal standard method to determine age from aspartic acid (Asp) racemization. D-Methionine (D-Met) and D-norleucine (D-Nleu) were tested as internal standards for the purpose of validating the derivatization and gas chromatographic measurements. Using a set of standard amino acids plus the internal standards in constant volume, calibration plots with reasonable linearity (R > 0.98) were constructed. Based on the analysis of sample chromatograms, D-Met appeared to meet the criteria for internal standards, hence it was selected for use in D- and L-Asp quantification. The correlation between dentin age and D-/L-Asp ratios from the peak areas as well as from the absolute concentrations was investigated. Correlation coefficients were calculated as 0.98 and 0.90, respectively. The slight decrease in accuracy was attributed to the conversion of D-Asp/D-Met ratios to concentrations employing the calibration curves figured from pure Asp. Because the application of the internal standard method produced reproducible and precise measurements, the employment of internal standards in age estimation based on Asp racemization appears to provide quality assurance by avoiding possible errors arising from sample preparation.

Adolescent↗

PubMed2003

Simultaneous determination of triflusal and its major active metabolite, 2-hydroxy-4-trifluoromethyl benzoic acid, in rat and human plasma by high-performance liquid chromatography.

A rapid, selective and sensitive high-performance liquid chromatography (HPLC) method was developed and validated for the simultaneous determination of triflusal and its major active metabolite, 2-hydroxy-4-trifluoromethyl benzoic acid (HTB), in rat and human plasma. HPLC analysis was carried out using a 5-microm particle size, C18-bonded silica column and acetonitrile-methanol-water (25:10:65, v/v/v) as the mobile phase and UV detection at 234 nm. Furosemide was used as the internal standard. The method involved extraction with an acetonitrile-chloroform mixture (60:40, v/v) and evaporation to dryness with nitrogen stream. The chromatograms showed good resolution and sensitivity and no interferences by plasma constituents. The mean absolute recovery for human plasma was 93.5 +/- 4.2% for triflusal and 98.5 +/- 3.1% for HTB. The lower limits of quantification of triflusal and HTB in human plasma were 20 and 100 ng/ml, respectively. The calibration curves in human plasma were linear over the concentration range 0.02-5.0 microg/ml for triflusal and 0.1-200.0 microg/ml for HTB with correlation coefficients greater than 0.999 and with inter- or intra-day coefficients of variation (CV) not exceeding 10.0%. This assay procedure was applied to the study of metabolite pharmacokinetics of triflusal and HTB in rat and human.

Animals↗

PubMed1999

Determination of candesartan cilexetil, candesartan and a metabolite in human plasma and urine by liquid chromatography and fluorometric detection.

Liquid chromatographic methods are described for the determination of a new effective anti-hypertensive drug candesartan (CV-11974), its prodrug candesartan cilexetil (TCV-116) and a metabolite, CV-15959 in human plasma and urine. The assays comprise liquid-liquid extraction and separation on a phenyl column with fluorometric detection. The methods give absolute recoveries of 70, 83 and 78% for candesartan cilexetil, candesartan and CV-15959, respectively, and the limit of quantification is 5, 1 and 3 nM of plasma (RSD < 20%), respectively. The methods were applied to plasma and urine samples from biopharmaceutical and clinical studies in man.

Antihypertensive Agents↗