Biomedical subjects

P Marquet

Publications and source records attributed to P Marquet.

At least 19 recordsLinked to original sources

PubMed2006

Multi-center evaluation of analytical performance of the microparticle enzyme immunoassay for sirolimus.

OBJECTIVES: This study evaluated the analytical characteristics of the new Abbott microparticle enzyme immunoassay (MEIA) for sirolimus. DESIGN AND METHODS: The protocol consisted of nine sections: evaluation of antibody specificity, linearity, detection limit, quantification limit, endogenous interferents, exogenous interferents, precision, proficiency testing panel, and method comparison. RESULTS: The mean analytical detection limit was 0.68 microg/L. The sirolimus concentration corresponding to a total CV of 20% was 1.5 microg/L. Linearity of response was demonstrated across the dynamic range of the assay. Total precision (CVs) at QC control levels from 5 to 22 microg/L ranged from 5.7 to 12.6%. Assay standardization was found to be in good agreement with LC/MS/MS as compared with target values for spiked sirolimus proficiency samples from an international sirolimus proficiency testing program. Good correlations (R values) of the immunoassay were observed in comparisons to LC/MS/MS. R values tended to be lower in comparisons with LC/UV methods. Across both LC-based methods and all study sites, there was approximately 25% overall positive slope bias due to cross reactivity of the MEIA antibody to metabolites of sirolimus. The assay cross-reactivity to metabolites of sirolimus parent drug ranged from 6 to 63%. Assay interferences were minimal with the exception of hematocrit, which presented a negative relationship to measured sirolimus concentration. CONCLUSIONS: The MEIA demonstrated acceptable analytical characteristics for use for routine monitoring of sirolimus immunosuppressive therapy, and is a viable alternative to HPLC-based methods for sirolimus monitoring.

Calibration↗

PubMed2006

Simultaneous determination of six dialkylphosphates in urine by liquid chromatography tandem mass spectrometry.

Dialkylphosphates (DAP) are urinary markers of the exposure to organophosphates pesticides. The aim of this study was to develop a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous quantitative determination of the following DAP: dimethylphosphate (DMP), dimethythiophosphate (DMTP), dimethyldithiophosphate (DMDTP), diethylphosphate (DEP), diethylthiophosphate (DETP) and diethyldithiophosphate (DEDTP). Dibutylphosphate (DBP) was used as internal standard. This method was based on a liquid-liquid extraction procedure, a chromatographic separation using an Inertsil ODS3 C18 column and mass spectrometric detection in the negative ion, multiple reaction monitoring (MRM) mode, following two ion transitions per compound. It yielded a limit of quantification of 2 microg/L for the six compounds and intra-assay coefficients of variation (CV%) lower than 20%. This method was applied to the analysis of urines samples from a small cohort of non-exposed volunteers. At least one of the six DAP was detected in each sample. This result confirmed the feasibility of a LC-MS/MS procedure for monitoring the general population exposure to some frequently employed organophosphate pesticides.

Adult↗

PubMed2006

A fully automated turbulent-flow liquid chromatography-tandem mass spectrometry technique for monitoring antidepressants in human serum.

Antidepressants belong to a variety of chemical and pharmacologic classes. Most require therapeutic drug monitoring, at least in certain circumstances, such as unexplained inefficacy or suspected toxicity. Several types of chromatographic methods have generally been used. This paper presents a fully automated, sensitive, and specific method for the therapeutic drug monitoring of 13 antidepressants of all classes (amoxapine, amitriptyline, citalopram, clomipramine, dothiepin, doxepin, fluoxetine, imipramine, maprotiline, mianserin, paroxetine, sertraline, trimipramine) and some of their respective active metabolites (nortriptyline, monodesmethylcitalopram, desmethylclomipramine, desipramine, norfluoxetine, desmethylmianserin, N-desmethylsertraline), based on the innovative turbulent-flow liquid chromatography (TFC) technology, coupled to tandem-mass spectrometry (MS/MS). The antidepressants were divided in two groups depending on their chromatographic properties, so that two injections would be necessary to screen all compounds (which is infrequent for therapeutic drug monitoring). Calibration curves ranged from 10 to 500 ng/mL. No significant memory effect was observed after the injection of a blank serum sample spiked at 500 ng/mL. The intra-assay and inter-assay precision CVs ranged from 0.4% to 12% and from 1% to 16%, respectively. The method was further validated by blindly analyzing Heathcontrol-Therapeutic Drugs Scheme samples (Cardiff Bioanalytical Services Ltd.) containing several antidepressants.

Antidepressive Agents↗

PubMed2006

[Treatment of pesticides determination requests in biological samples: some problems frequently encountered ].

Currently, the determination of pesticides in human fluids is complex. Our scientific knowledge on pesticide intoxication is fragmentary. This leads to numerous difficulties regarding the diagnosis, the analysis request, the choice of the analytical technique, the interpretation of the results. Consequently the waiting time to provide a result is not compatible with the initiation of a treatment in the intoxicated patients. Very few information about Human intoxication with pesticides is available from the literature. In this context, we tried to acquire our own experience. We chose to deal with all pesticides intoxication suspicions received, in collaboration with clinicians. We are presenting the main problems we encounter.

Hair↗

PubMed2004

Population pharmacokinetic modeling of oral cyclosporin using NONMEM: comparison of absorption pharmacokinetic models and design of a Bayesian estimator.

There have been very few population pharmacokinetic (PopPK) studies and Bayesian forecasting methods dealing with cyclosporin (CsA) so far, probably because of the difficulty of modeling the particular absorption profiles of CsA. The present study was conducted in stable renal transplant patients treated with Neoral and employed the NONMEM program. Its goals were (1) to develop a population pharmacokinetic model for CsA based on an Erlang frequency distribution (which describes asymmetric S-shaped absorption profiles) combined with a 2-compartment model; (2) to compare this model with models combining a time-lag parameter and either a zero-order or first-order rate constant and with a model based on a Weibull distribution; and (3) to develop a PK Bayesian estimator for full AUC estimation based on that "Erlang model." The PopPK model was developed in an index set of 70 patients, and then individual PK parameters and AUC were estimated in 10 other patients using Bayesian estimation. The "Erlang" model best described the data, with mean absorption time (MAT), apparent clearance (CL/F), and apparent volume of the central compartment (Vc/F) of 0.78 hours, 26.3 L/h, and 76 L, respectively (interindividual variability CV = 33, 30, and 48%). Bayesian estimation allowed accurate prediction of systemic exposure using only 3 samples collected at 0, 1, and 3 hours. Regression analysis found no significant difference between the predicted and observed concentrations (10 per patient), and AUC(0-12) were estimated with a nonsignificant bias (0.6 to 8.7%) and good precision (RMSE = 5.3%). In conclusion, the Erlang distribution best described CsA absorption profiles, and a Bayesian estimator developed using this model and a mixed-effect PK modeling program provided accurate estimates of CsA systemic exposure using only 3 blood samples.

Area Under Curve↗

PubMed2003

Comparison of a preliminary procedure for the general unknown screening of drugs and toxic compounds using a quadrupole-linear ion-trap mass spectrometer with a liquid chromatography-mass spectrometry reference technique.

Liquid chromatography-tandem mass spectrometry (LC-MS-MS) might be a complement to GC-MS and HPLC-diode array detection for the general unknown screening (GUS) of drugs and toxic compounds, particularly when using information- or data-dependent acquisition (IDA or DDA), an auto-adaptive MS-MS product-ion scan mode where, at each unit time, the m/z ratios above a given intensity threshold are selected for fragmentation. A new quadrupole-linear ion-trap mass spectrometer (LC-QqQlinear ion-trap) was evaluated for GUS using IDA. For the first detection step (so-called "survey scan") the single quadrupole "enhanced" MS mode (EMS), where ions are accumulated then filtered in the Q3-linear ion-trap, was used. The so-called "enhanced" parent ion scan mode (EPI) used at two alternated fragmentation energies gave the best signal intensity and the best mass spectral information when adding mass spectra obtained in low and high fragmentation conditions, respectively, both in the positive (+20 and +50 eV) and negative (-15 and -40 eV) modes. Solid-phase extracts of serum spiked with eight test compounds (chosen for their retention times distributed along the 30-min long chromatogram and for ionising in both the positive and negative modes) were analysed in parallel with this LC-MS-MS technique and with a reference LC-MS method run on a single-quadrupole instrument where low and high in-source fragmentation conditions in the positive and the negative ion modes are alternated. A C(18), 5 microm (150 x 1 mm I.D.) column and a gradient elution of acetonitrile in pH 3, 2 mM ammonium formate, were used for both. Higher signal-to-noise ratios were obtained with the LC-QqQlinear ion-trap instrument than with the reference technique, resulting in mass spectra devoid of contaminant ions and at least as informative as the reconstructed single-MS spectra. After optimisation of the IDA intensity threshold for the detection of tiny chromatographic peaks in noise, five out of the eight compounds (milrinone, lorazepam, fluometuron, piretanide and warfarin) could be unambiguously identified at the concentration of 0.1 mg/l in serum, in the positive or negative modes, or in both, versus only two by LC-MS. All of them could be identified at 1 mg/l by both techniques. These preliminary results show that the sensitivity and mass structural information brought by this new LC-QqQlinear ion-trap instrument may help design an efficient toxicological GUS procedure.

Chromatography, Liquid↗

PubMed2003

Comparison of the prevalence of alcohol, cannabis and other drugs between 900 injured drivers and 900 control subjects: results of a French collaborative study.

A collaborative case-control study was conducted in France in order to determine the prevalence of alcohol, cannabinoids, opiates, cocaine metabolites, amphetamines and therapeutic psychoactive drugs in blood samples from drivers injured in road accidents and to compare these values with those of a control population. Recruitment was performed in emergency departments of six university or general hospitals and comprised 900 drivers involved in a non-fatal accident and 900 patients (controls) who attended the same emergency units for a non-traumatic reason. Drivers and controls were matched by sex and age. Alcohol was determined by flame ionization-gas chromatography, drugs of abuse (DOA) by gas chromatography-mass spectrometry with the same analytical procedures in the six laboratories, and medicines by high performance liquid chromatography with diode array detection. Blood alcohol concentration exceeding 0.5 g/l (i.e. the legal French threshold) was found in 26% of drivers and 9% of controls. In the 18-27 years age range, alcohol was the only toxic found in blood samples of 17% drivers and 5% controls, leading to an odds-ratio (OR) of 3.8. A significant relationship was found between alcohol blood concentrations and OR values. All age groups confounded, the main active substance of cannabis, Delta(9) tetrahydrocannabinol (THC), was found in 10% of drivers and 5% of controls. In the less than 27 years old, THC (>1 ng/ml) was detected alone in the blood of 15.3% drivers and of 6.7% controls, giving OR=2.5, whereas there was no link between THC blood concentrations and OR value. THC was found alone in 60% of cases and associated with alcohol in 32%, with OR=4.6 between drivers and controls for this association. The difference in morphine prevalence between drivers (2.7%) and controls (0.03%) was highly significant (P<0.001), with OR=8.2. The number of positive cases for amphetamines and cocaine metabolites was too low for reaching any interpretation. The most frequently observed psychoactive therapeutic drugs were by far benzodiazepines, that were found alone in 9.4% of drivers and 5.8% of controls, which led to OR=1.7 (P<0.01). This study demonstrates a higher prevalence of opiates, alcohol, cannabinoids and the combination of these last two compounds in blood samples from drivers involved in road accidents than in those from controls, which suggests a causal role for these compounds in road crashes.

Accidents, Traffic↗

PubMed2003

Limited sampling strategies using Bayesian estimation or multilinear regression for cyclosporin AUC(0-12) monitoring in cardiac transplant recipients over the first year post-transplantation.

OBJECTIVE: The aim of this study was to develop routinely applicable limited sampling strategies for assessing cyclosporin (CsA) AUC(0-12 h), and possibly other exposure indices such as AUC(0-4 h) and C(max), in heart transplant patients over the first year post-transplantation. METHODS: First, the individual pharmacokinetics (PKs) of 14 adult heart-transplant patients receiving Neoral were assessed at three post-transplantation periods, at the end of the first week (W1), the third month (M3) and the first year (Y1). To fit blood concentrations, a PK model specially developed for oral CsA was applied. Second, two statistical methods were compared for AUC(0-12 h) estimation using a limited sampling strategy (maximum of three blood samples): multiple regression analysis (MR) and Bayesian estimation (BE). RESULTS: No significant difference was observed between the individual PK parameters at M3 and Y1, so population modelling was performed taking as a whole the concentration data collected at M3 and Y1. On the contrary, a significant difference ( P<0.05) was found for the C2/dose ratio between W1 and M3 and between W1 and Y1 (mean+/-SD =5.47+/-2.33; 7.78+/-1.05; 6.98+/-2.17 ml(-1 )for W1, M3 and Y1, respectively). Also, C(max)/dose and A were found significantly lower at W1 than at M3 ( P<0.01 and P<0.005, respectively), while lambda(1) was significantly higher at W1 than at both M3 and Y1 ( P<0.01). Using three sampling times (t0 h, t1 h and t3 h), BE allowed an accurate prediction of AUC(0-12 h) (mean bias =3.06+/-12.16%; +1.50+/-1.61%; and -0.20+/-11.42% at W1, M3 and Y1, respectively), AUC(0-4 h )and C(max). MR led to satisfactory estimation of AUC(0-12 h) using only two blood samples collected 2 h and 6 h post-dose (R=0.956-0.993; bias =-5.22 to +4.41; precision =6.38 to 9.90%), but this method is unable to estimate any other exposure index and requires strict respect of sampling times, contrary to BE. CONCLUSION: Neoral monitoring based on full or abbreviated AUC is possible using BE or MR in heart transplant patients over the first year post-transplantation. BE provides a good description of the individual PK profiles and thus might be useful not only in case of potential discrepancies between C2 and clinical findings, but also for clinical trials aimed at finding optimum PK monitoring in heart recipients.

Area Under Curve↗

PubMed2003

Bayesian forecasting of oral cyclosporin pharmacokinetics in stable lung transplant recipients with and without cystic fibrosis.

The aims of the current study were (1) to study Neoral pharmacokinetics (PK) in stable lung recipients with or without cystic fibrosis (CF), (2) to compare Neoral PK between these two groups, and (3) to design Bayesian estimators for PK forecasting and dose adjustment in these patients using a limited number of blood samples. The individual PK of 19 adult lung transplant recipients, 9 subjects with CF and 10 subjects without CF, were retrospectively studied. Three profiles obtained within 5 days were available for each patient. A PK model combining a gamma distribution to describe the absorption profile and a two-compartment model were applied. Different exposure indices were estimated using nonlinear regression and Bayesian estimation. The PK model developed reliably described the individual PK of Neoral in lung transplant patients with and without CF, and the values of the first and second half-lives were different in these two populations (lambda(1) = 4.14 +/- 3.01 vs. 2.16 +/- 1.75 h(-1); P < 0.01; lambda(2) = 0.36 +/- 0.11 vs. 0.49 +/- 0.12 h(-1); P < 0.01), while the mean absorption time and standard deviation of absorption time tended to be less in patients with cystic fibrosis (P < 0.1). Also, the patients with CF required higher doses than those without CF to achieve similar drug exposure. Consequently, population modeling was performed in CF and non-CF patients separately. Bayesian estimation allowed accurate prediction of AUC(0-12), AUC(0-4), C(max), and T(max) using three blood samples collected at T0h, T1h, and T3h in both groups. This study demonstrated the applicability and good performance of the PK model previously developed for oral cyclosporin and of the MAP Bayesian estimation of cyclosporin systemic exposure in CF and non-CF patients. Moreover, it is the first to propose a monitoring tool specifically designed for cyclosporin monitoring in patients with CF.

Administration, Oral↗

PubMed2002

Absolute bioavailability of midazolam after subcutaneous administration to healthy volunteers.

AIMS: Midazolam is given intravenously for induction of anaesthesia and conscious sedation and by subcutaneous infusion in patients in palliative care units. The objective of the present study was to determine the absolute bioavailability of subcutaneous midazolam and its pharmacokinetics in young, healthy, male volunteers. METHODS: Eighteen volunteers were given single doses of 0.1 mg kg-1 midazolam i.v. and s.c. after a wash-out period of 7-15 days in an open-label, randomized, cross-over study. Blood samples were collected up to 12 h post-infusion. Plasma concentrations of midazolam and of its two metabolites, 1'-OHM and 4-OHM, were assessed using an h.p.l.c.-MS method (LOQ 0.5 ng ml-1 for each analyte). Vital signs, cardiac parameters and oximetry were monitored. Local tolerance was determined and adverse events were also monitored. RESULTS: After s.c. infusion t(max) and C(max) were 0.51 +/- 0.18 h and 127.8 +/- 29.3 ng ml-1 (mean +/- s.d.), respectively. No statistically significant difference was detected in AUC(0, infinity ) after i.v. and s.c. administration. The mean (+/- s.d.) absolute bioavailability of subcutaneous midazolam was 0.96 (+/- 0.14) (CI 0.84, 1.03). Mean (+/- s.d.) t1/2 was similar after s.c. (3.2 (+/- 1.0) h) and i.v. infusion (2.9 (+/- 0.7) h), although a statistically significant difference was reached (P < 0.05). Mean CL and V of i.v. midazolam were 4.4 +/- 1.0 ml min-1 kg-1 and 1.1 +/- 0.2 l kg-1 (mean +/- s.d.), respectively. Plasma concentrations of 1'-OHM were higher than those of 4-OHM. Few mild and transient adverse events were noted and there were no clinically significant effects on EEG, blood pressure and laboratory parameters. CONCLUSIONS: This study has shown that subcutaneous midazolam has excellent bioavailability and that administration of midazolam by this route could be preferable when the intravenous route is inappropriate.

Adult↗

PubMed2002

[New drugs at "rave parties": ketamine and prolintane].

"Rave parties", all-night dance parties based on "techno" music, represent an increasing phenomenon in France. "Rave drugs" refers to a wide variety of drugs used by the young participants owing to their hallucinogenic or stimulant effects. Uncertainties about the sources of these substances, the possible contaminants and the multiplicity of the associations make it difficult to evaluate the toxic consequences that might be expected in this particular context. This report presents toxicological cases documented by analytical findings in which two pharmacological agents abused in "rave parties" in South-West of France were found. The day following a party, a 17 year-old girl showed a confused state with drowsiness and hallucinations. She confessed having consumed a white powder sold as "ecstasy", that sample analysis identified as pure ketamine. Ketamine is an anaesthetic agent primarily used in veterinary medicine and paediatrics. This drug seems to be abused, mainly by the intranasal route, owing to its hallucinogen effects. Its used in "rave-party" appears to be marked by unsuspected consumption. All long another party, a large quantity of orange tablets were sold and abused by several participants. Analysis performed on some fragments of these tablets revealed the presence of prolintane and ascorbic acid. Prolintane, an amphetamine-related substance, is a central nervous system stimulant. This compound is "freely" available in Spain in combination with several vitamins, under the form of tablets with orange coating named "Katovit" and sold at low price: 1.93 [symbol: see text]/20 tablets (200 mg of prolintane).

Adolescent↗

PubMed2001

Sensitive and specific multiresidue methods for the determination of pesticides of various classes in clinical and forensic toxicology.

Original and sensitive multiresidue methods are presented for the detection and quantitation, in human biological matrices, of 61 pesticides of toxicological significance in human. These methods involved rapid solid-phase extraction using new polymeric support (HLB and MCX) OASIS cartridges. Gas chromatography-mass spectrometry (GC-MS) was used for volatile (organophosphate, organochlorine, phtalimide, uracil) pesticides and liquid chromatography-ionspray-mass spectrometry (LC-MS) for thermolabile and polar pesticides (carbamates, benzimidazoles). Acquisition was performed in the selected ion monitoring (SIM) mode. Extraction recovery varied owing to the nature of pesticides, but was satisfactory for all. Limits of detection (LODs) and limits of quantitation (LOQs) ranged, respectively, from 2.5 to 20 and from 5 to 50ng/ml. An excellent linearity was observed from LOQs up to 1000ng/ml for all the pesticides studied. The proposed procedures yielded reproducible results with good inter-assay accuracy and precision. A few cases of intoxication are presented to demonstrate the diagnostic interest of these methods: in two cases were determined lethal concentrations of endosulfan and carbofuran; in four other cases, the procedures helped diagnose intoxication with, respectively, parathion-ethyl, the association of bromacil and strychnine, bifenthrin and aldicarb.

Adult↗

PubMed2001

Determination of N-acetylation phenotype using caffeine as a metabolic probe and high-performance liquid chromatography with either ultraviolet detection or electrospray mass spectrometry.

A rapid, sensitive method using liquid chromatography-electrospray mass spectrometry (LC-ES-MS) was developed and evaluated for the simultaneous quantitative determination of caffeine metabolites 1U, 1X and AAMU in human urine. This method involved a simple dilution of urine samples. The chromatographic separation was achieved on a C18 reversed-phase column using a gradient of acetonitrile in 2 mM, pH 3.0 ammonium formate as mobile phase. After ionisation in an electrospray source, mass spectrometric detection was performed in the negative ion, selected ion monitoring mode. This method yielded acceptable accuracy and precision within the range 0.25-50 microg/ml. This analytical method was applied to investigate the N-acetylator phenotype of HIV-infected patients and compared with high-performance liquid chromatography with UV detection. Its specificity was better, which appeared to be absolutely necessary to prevent errors in metabolic ratios and phenotype interpretation.

Acetylation↗

PubMed2001

Multiresidue determination method for organophosphorus pesticides in serum and whole blood by gas chromatography-mass-selective detection.

This paper describes a rapid, specific and sensitive method for the determination of 29 organophosphorus pesticides in blood and serum, involving a rapid solid-phase extraction procedure using Oasis HLB cartridges and gas chromatography coupled to mass-selective detection. The ionization was performed by electron Impact and acquisition in the single ion monitoring mode followed three specific ions per analyte. Extraction recoveries were satisfactory and ranged between 40 and 108% in blood and serum. Limits of detection ranged from 5 to 25 ng/ml and limits of quantitation (LOQs) ranged from 10 to 50 ng/ml, in blood and serum. An excellent linearity was observed from these LOQs up to 1000 ng/ml. Intra- and inter-assay precision and accuracy were satisfactory for most of the pesticides analyzed.

Gas Chromatography-Mass Spectrometry↗

PubMed2001

Sensitive determination of vinorelbine and its metabolites in human serum using liquid chromatography-electrospray mass spectrometry.

A liquid chromatography-electrospray mass spectrometry method was developed for the quantitation of vinorelbine (VNB) and two metabolites, vinorelbine N-oxide (VNO) and deacetyl vinorelbine (DAV) in human serum. The limits of quantitation (LOQ) reached 0.5 ng/ml for both VNB and VNO and 1 ng/ml for DAV. The method was proved linear in the range of LOQs up to 1000 ng/ml, and extraction recovery was 80% on average for the three compounds. It was applied to the pharmacokinetic monitoring of vinorelbine and, for the first time, to the detection of VNO in the serum of patients suffering from non-small-cell lung cancer.

Antineoplastic Agents, Phytogenic↗

PubMed2001

Application of a gamma model of absorption to oral cyclosporin.

BACKGROUND: Some drugs, such as cyclosporin, exhibit flat and delayed absorption profiles, with a correlation between the delay and the peak width. Such profiles can be described by an absorption model in which the absorption rate is derived from a gamma distribution (of which the classical first-order absorption model is a special case). OBJECTIVE: To develop a model for the pharmacokinetics of extravascular administration of cyclosporin and apply it to a study of the pharmacokinetics of cyclosporin microemulsion in stable renal transplant recipients. PATIENTS AND PARTICIPANTS: 21 renal transplant patients receiving oral cyclosporin microemulsion 75 to 175 mg twice daily. METHODS: The equation of the plasma concentration-time curve after oral administration was expressed as a convolution product between the absorption rate and a multi-exponential impulse response. The convolution integral was computed analytically and expressed in terms of the incomplete gamma function. Cyclosporin was assayed by liquid chromatography/mass spectrophotometry. The model was fitted by nonlinear regression, using a specially developed program. RESULTS: The gamma model yielded a good fit in all of the 21 patients studied. Attempts to fit the same data by a classical exponential with lag-time model failed in most patients. CONCLUSIONS: This model could simplify the Bayesian monitoring of cyclosporin therapy.

Area Under Curve↗

PubMed2001

Fatal intoxications with chloral hydrate.

An alcoholic man, treated with chloral hydrate (CH) syrup to which he was dependent, was discovered comatose and in respiratory arrest. Death occurred on the ninth day of hospitalization following cerebral oedema. A woman, alcohol addicted, depressed, and epileptic was admitted in the Intensive Care Unit with heart and respiratory failure following CH absorption. She died three days later after a deep coma. In these two cases, CH intoxication was confirmed by toxicological analysis: CH and its major metabolite, trichloroethanol (TCE), were identified and determined in serum and urine using headspace-capillary gas chromatography-mass spectrometry. The concentrations measured were compared with those found in previously published fatalities. The analytical method used can be proposed for both clinical and forensic cases.

Adult↗

PubMed2000

High-performance liquid chromatographic determination of tianeptine in plasma applied to pharmacokinetic studies.

An improved analytical method for the quantitative measurement of tianeptine and its main metabolite MC5 in human plasma was designed. Extraction involved ion-paired liquid-liquid extraction of the compounds from 1.0 ml of human plasma adjusted to pH 7.0. HPLC separation was performed using a Nucleosil C18, 5 microm column (150x4.6 mm I.D.) and a mixture of acetonitrile and pH 3, 2.7 g l(-1) solution of sodium heptanesulfonate in distilled water (40:60, v/v) as mobile phase. UV detection was performed using a diode array detector in the 200-400 nm passband, and quantification of the analytes was made at 220 nm. For both tianeptine and MC5 metabolite, the limit of quantitation was 5 microg l(-1) and the calibration curves were linear from 5 to 500 microg l(-1). Intra- and inter-assay precision and accuracy fulfilled the international requirements. The recovery of tianeptine and its metabolite from plasma was, respectively, 71.5 and 74.3% at 20 microg l(-1), 71.2 and 70.8% at 400 microg l(-1). The selectivity of the method was checked by verifying the absence of chromatographic interference from pure solutions of the most commonly associated therapeutic drugs. This method, validated according to the criteria established by the Journal of Chromatography B, was applied to the determination of tianeptine and MC5-metabolite in human plasma in pharmacokinetic studies.

Antidepressive Agents, Tricyclic↗