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G Lachâtre

Publications and source records attributed to G Lachâtre.

At least 37 records · Page 2Linked to original sources
PubMed1999

Liquid chromatography-electrospray mass spectrometry multi-residue determination of pesticides in apples and pears.

This paper describes a rapid, specific and sensitive multi-residue method for the routine quantitative analysis of pesticides of several classes used for the treatment of apples and pears, down to their respective maximum residue limits (MRLs). It involves a rapid extraction procedure and liquid chromatography coupled to electrospray mass selective detection. Seven pesticides were extracted at pH 4.5 with a mixture of acetone-dichloromethane-hexane (50:20:30, v/v/v). Ionization was performed at atmospheric pressure in an electrospray-type source and detection was carried out using the selected ion monitoring (SIM) mode. Extraction recoveries were between 55 and 98% except for methylthiophanate (< 20%). Limits of detection (LODs) and limits of quantitation (LOQs) ranged, respectively, from 0.01 to 0.02 mg/kg and from 0.02 to 0.05 mg/kg, with relative standard deviation (R.S.D.) less than 19%. An excellent linearity was observed for LOQs up to 5 mg/kg. Intermediate ("inter-assay") precision and accuracy were satisfactory. The method was applied to many fruit samples intended for commercialization.

Chromatography, High Pressure Liquid↗
PubMed1998

Multiresidue determination of pesticides in apples and pears by gas chromatography-mass spectrometry.

This paper describes a rapid, specific and sensitive multiresidue method for the routine analysis of several classes of pesticides used for the treatment of apples and pears, involving a rapid extraction procedure at pH 4.5 with a mixture of acetone-dichloromethane-hexane (50:20:30, v/v/v) and gas chromatography coupled to mass-selective detection, in order to achieve quantitative analysis down to their respective maximum residue limit. Extraction recoveries were between 55 and 98%. Limits of detection and limits of quantitation ranged respectively, from 0.01 to 0.05 mg/kg and from 0.02 to 0.1 mg/kg. Intra-assay relative standard deviation was less than 19% for all compounds. An excellent linearity was observed from these LOQs up to 500 mg/kg. Intermediate (inter-assay) precision and accuracy were satisfactory. The method has been applied to many fruit samples intended for commercialisation.

Fruit↗
PubMed1998

Relationship between psychotropic drugs and thyroid function: a review.

Some widely used psychoactive drugs, such as tricyclic antidepressants and antipsychotic phenothiazines exhibit iatrogenic effects on the thyroid. These side effects may arise from interactions at different steps of thyroid hormone biosynthesis. These drugs can induce a change in iodine capture by thyroid cells or can complex iodine, making it unavailable for thyroid hormone synthesis and thus decreasing thyroid hormone blood levels; they can also inhibit thyroid peroxidase activity and thus T3 and T4 synthesis or enhance deiodination of T4 to T3 or to Rt3 by stimulation of deiodinase activity. Moreover, tricyclic antidepressants interfere with the hypothalamic-pituitary-thyroid axis via the noradrenergic or serotonergic systems and might therefore decrease T4 or T3 blood levels, respectively. Phenothiazines can induce autoimmune hypothyroidism, as shown by an increase in the expression of the major histocompatibility complex antigen and by a production of antithyroglobulin or antithyroperoxidase antibodies. However, all these mechanisms are only speculative in humans, as they have only been demonstrated in vitro or in animal experiments. Clinically, thyroid function and affective disorders are closely linked. On one hand, the therapeutic response to antidepressants could be influenced by the thyroid status; on the other hand, the larger the thyroxin decrease induced by antidepressants, the better the therapeutic effect might be. Moreover, cotreatment with thyroid hormones and antidepressant drugs could allow either a decrease in the rate of treatment failure or a faster recovery from depression. As antipsychotic or antidepressant treatments are administered over long periods in humans, their thyroid toxic effects must be taken seriously.

Animals↗
PubMed1998

Bayesian pharmacokinetic estimation of vinorelbine in non-small-cell lung cancer patients.

OBJECTIVE: To develop a population pharmacokinetics of vinorelbine in a population of non-small-cell lung cancer (NSCLC) patients using a Bayesian estimation in order to calculate for any further patient, individual pharmacokinetic parameters from few blood samples. METHODS: Vinorelbine was given by a 15-min infusion (30 mg x m(-2)) to eight patients with NSCLC. Its serum concentration was determined by HPLC and its pharmacokinetics was described by a three-compartment open model with elimination from the central compartment. Volume of the central compartment (V1) and rate constants (k10, k12, k21, k13, k31) were selected as population pharmacokinetic parameters and computed by non-linear regression (two-step approach) from 14 to 18 concentration measurements per course. Subsequently, these parameters were used by the Bayesian estimator to calculate individual pharmacokinetics from only 2 or 3 measured concentrations. RESULTS: The population mean values (CV%) of V1, k10, k12, k21, k13, k31, CL, t1/2gamma were respectively 21 l (55%), 3.2 h(-1) (29%), 7.7 h(-1) (74%), 1.3 h(-1) (67%), 4.7 h(-1) (53%), 0.04 h(-1) (20%), 57 l x h(-1) (31%) and 43 h (36%). The comparison of results obtained from the Bayesian estimator and from the three-compartment model showed that CL and t1/2gamma were well predicted (relative deviation: +/- 12 to 22%) by the Bayesian method using only two blood samples. CONCLUSION: We demonstrated that Bayesian estimation allows, at minimal cost and minimal disturbance for the patient, the determination of several vinorelbine pharmacokinetic parameters and therefore dose adaptation from as few as two drug concentrations, measured at 6 h and 24 h after infusion.

Aged↗
PubMed1998

Screening procedure for 21 amphetamine-related compounds in urine using solid-phase microextraction and gas chromatography-mass spectrometry.

A specific, sensitive, and rapid procedure for the screening of 21 amphetamine-related compounds in urine is developed using solid-phase microextraction (SPME) and gas chromatography-mass spectrometry. Very clean extracts are obtained in one step with SPME using silica fibers coated with a 100-micron polydimethylsiloxane stationary phase. Temperature, time, pH, and salt saturation are optimized to obtain consistent extraction. An excellent chromatographic separation of the underivatized analytes is obtained with a specially treated nonpolar capillary column (Supelco PTA-5, 30 m x 0.32-mm i.d., 0.5-micron film thickness) dedicated to amino compounds. Selected ion monitoring of three fragments per analyte and one for each of the three deuterated internal standards elicits a high selectivity and detection limits between 1 and 50 ng/mL (i.e., low enough to verify positive results obtained with immunochemical assays). The method is linear in a narrow range (from the detection limit up to 500 ng/mL) when all the amphetamines are assayed together but shows a good linearity up to 2000 ng/mL when the molecules are determined individually. Repeatability is not satisfactory for all compounds but could probably be improved by strictly controlling the extraction time (e.g., by automating the whole procedure using an autosampler). The use of SPME reduces the interference due to urinary low-volatility organic compounds and avoids the risks related to the use of organic solvents. To our knowledge, this technique is the first one allowing the sensitive determination of such a number of amphetamine analogs.

Amphetamine↗
PubMed1998

Thyroid accumulation and adverse effects of imipramine and desipramine in rats after long-term administration.

The respective adverse effects of imipramine and desipramine on serum thyroid hormone levels and their accumulation in thyroid were investigated in male Wistar rats. Two groups of 30 rats were gavaged for 4 weeks with 30 mg/kg/day imipramine hydrochloride (IMI) or desipramine hydrochloride (DESI), while the control group (12 rats) received the arabic gum vehicle only. In the IMI-treated group, the serum thyroxine (T4) level significantly decreased (by 13%) and IMI and its metabolite DESI were accumulated in the thyroid, as pointed out by mean thyroid-to-serum concentration ratios close to 12 and 8, respectively. In the DESI-treated group, the mean thyroid-to-serum concentration ratio of the drug was close to 14, and significant decreases in both serum T4 (-20%) and triiodothyronine serum levels (-14%) were found. The accumulation of antidepressant drugs in the thyroid was more pronounced and the thyroid serum levels were even lower after DESI administration than after IMI administration. These results are in favour of an antithyroid action of IMI and DESI due to the formation of a complex in the thyroid between molecular iodine and the drugs or metabolites.

Animals↗
PubMed1998

Influence of biological variables upon pharmacokinetic parameters of intramuscular methotrexate in rheumatoid arthritis.

The pharmacokinetics of methotrexate were studied in 22 patients receiving 5-15 mg per week in a single i.m. administration for rheumatoid arthritis. The data consisted of 3 plasma levels per patient, taken at 2, 6, and 12 hours after the administration. The concentration of methotrexate was determined by fluorescence polarization immunoassay. The pharmacokinetic parameters of a 2-compartment model were determined by Bayesian estimation using the population values of Bressolle et al. [1996]. The fitted parameters were: total plasma clearance of methotrexate (CL), first-order absorption constant (ka), volume of central compartment (V1), and transfer constants between the 2 compartments (k12 and k21). Additional parameters were derived from the fitted ones: maximal concentration (Cmax), time to maximum (tmax), volume of distribution at steady-state (Vss), and terminal half-life (t1/2). Twenty-one biological covariates were considered to explain the interpatient variability. The relationships between these covariates and the pharmacokinetic parameters were investigated by principal component analysis and multiple regression analysis. About 90% of the variability of CL were explained by 4 variables (sex, age, height and serum creatinine). About 50%-70% of the variability of the other pharmacokinetic parameters were explained by a set of covariates including age, height, creatinine, creatinine clearance, and dose. The effect of dose was noticed mainly on k12, Vss, and t1/2, thus suggesting that the transfer of the drug from plasma to tissues may be nonlinear. The possibility of predicting CL with a good precision would facilitate the computation of dosage regimens in these patients.

Adult↗
PubMed1998

Is there an optimal time to administer methotrexate in the treatment of rheumatoid arthritis?

OBJECTIVE: To determine the optimal time to administer methotrexate (MTX) in rheumatoid arthritis (RA). METHODS: In a crossover study 23 patients were administered MTX intramuscularly at either 10 AM or 6 PM. A 2 week interval separated the 2 injections. MTX concentrations were measured using a fluorescence polarization immunoassay. Pharmacokinetic variables were estimated using a Bayesian approach. The morning and evening schedules were compared using analysis of variance to determine the optimal time of injection. RESULTS: No statistical difference was found in the pharmacokinetics of MTX according to hour of injection. A difference in the creatinine clearance, however, was observed in the samples obtained at noon and 8 PM, but clearance of MTX was unchanged. CONCLUSION: Pharmacokinetic variables suggest that MTX can be administered either in the morning (10 AM) or evening (6 PM) in the treatment of RA.

Adult↗
PubMed1997

Simultaneous determination of amphetamine and its analogs in human whole blood by gas chromatography-mass spectrometry.

A sensitive and specific gas chromatography-mass spectrometry (GC-MS) method for the determination of amphetamine (AM), methamphetamine (MA), methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA) and methylenedioxyethylamphetamine (MDEA) in whole blood was designed, using the respective pentadeuterated analogs of the analytes as internal standards (I.S.). After alkalinisation of blood samples, the amphetamines were extracted using diethyl ether, derivatized with heptafluorobutyric anhydride, then purified by successive washings with deionized water and 4% NH4OH. Extraction recoveries were 85.2% for AM, 90.9% for MA, 76.5% for MDA, 84.1% for MDMA and 63.6% for MDEA. Chromatographic separation was performed on a non-polar 30 m x 0.32 mm HP 5 MS capillary column using a temperature program. Detection was carried out in the electron-impact, selected ion-monitoring mode, using three mass-to-charge ratios for each analyte and one for each I.S. Limits of detection ranged from 0.5 to 8 ng/ml and limits of quantification were 10 ng/ml for AM, MDMA and MDEA; 20 ng/ml for MA; and 50 ng/ml for MDA. The method was linear from this limit up to 1000 ng/ml for all analytes, with good intra-assay precision and good intermediate precision and accuracy over these ranges. There was no interferences from other sympathomimetic drugs such as ephedrine, norephedrine or methoxyphenamine. This method is thus suitable for clinical and forensic toxicology, as well as for doping control.

Amphetamines↗
PubMed1997

Sensitive microanalysis of imipramine and desipramine in single rat thyroids by gas chromatography-mass spectrometry.

A new sensitive method for the quantitative determination of imipramine and desipramine in single rat thyroids using gas chromatography-mass spectrometry with selected ion monitoring, after enzymatic hydrolysis and liquid-liquid extraction has been developed. The technique was deemed suitable for microanalysis of single rat thyroids and for other solid tissues, using smaller sample sizes than usually required for traditional determination methods. The quantification was linear from 10 to 200 nmol/l (i.e., from 0.25 to 5 microg/g) for imipramine and from 100 nmol/l to 2000 nmol/l (i.e., from 2.4 to 47 microg/g) for desipramine, and the limits of detection (less than 25 ng/g tissue for both compounds) were better than those previously reported. Recoveries, repeatability and reproducibility of this technique were satisfactory. It has been successfully applied in a preliminary study of the concentration-time profiles of imipramine and desipramine in the thyroid of rats treated with either of these drugs.

Animals↗
PubMed1997

Determination of LSD and N-demethyl-LSD in urine by liquid chromatography coupled to electrospray ionization mass spectrometry.

A sensitive and highly specific method for the determination of LSD and N-demethyl-LSD in urine, using combined liquid chromatography and mass spectrometry (LC-MS) with electrospray ionization, has been developed. Extrelut-3 extraction cartridges were used for a basic sample clean-up. Elution was obtained by toluene-diethyl ether (60:40, v/v). A Nucleosil C18 (150 X 1 mm I.D.) reversed-phase column was used for the chromatographic separation, together with a mixture of 2 mM ammonium formate buffer (pH 3) and acetonitrile (70:30, v/v) as mobile phase. Recoveries were 93 and 80%, detection limits 0.025 and 0.035 ng/ml for LSD and N-demethyl-LSD, respectively. Intra-assay precision, studied at four concentrations, was better than 9% at the ng/ml range and better than 14% at 0.10 ng/ml for both compounds. Limits of quantitation were 0.05 and 0.10 ng/ml for LSD and N-demethyl-LSD, respectively. Reproducibility was good and linearity excellent for LSD in the range from 0.05 to 20 ng/ml (r>0.9999, n=7).

Chromatography, High Pressure Liquid↗
PubMed1997

Determination of haloperidol and its reduced metabolite in human plasma by liquid chromatography-mass spectrometry with electrospray ionization.

A sensitive and accurate liquid chromatographic-electrospray mass spectrometric (LC-ES-MS) method for the determination of haloperidol (H) and reduced haloperidol (RH) in human plasma is presented, using chlorohaloperidol as the internal standard. A 2-ml volume of plasma was subjected to basic (NaOH) extraction, acid (HCl) back-extraction, acid wash and basic (NaOH) re-extraction. The extraction solvent was hexane-isoamyl alcohol (99:1, v/v) for the whole procedure. A Nucleosil C18 column (150 x 1 mm) was used for high-performance liquid chromatography, together with 2 mM HCOONH4-acetonitrile (55:45, v/v; pH 3.0) as the mobile phase. For each drug, four characteristic ions were monitored. Linearity was assessed in the ranges 0.1-50 and 0.25-50 ng/ml for H and RH, respectively. Recoveries were 58 and 70% and detection limits were 0.075 and 0.100 ng/ml for H and RH, respectively. Correlation coefficients were better than 0.999 for both compounds. R.S.D.s for repeatability and reproducibility at 0.25 ng/ml were 11.1 and 8.5% for H and 9.4 and 11.2% for RH, respectively. One of the main advantages of (LC-ES-MS) over other detection systems is the increase in selectivity obtained by monitoring three ions of confirmation for each of the drugs.

Antipsychotic Agents↗
PubMed1997

Buprenorphine withdrawal syndrome in a newborn.

A pregnant woman who was addicted to heroin rapidly withdrew from illicit drugs after the onset of a 4 mg/day buprenorphine treatment. In the newborn's blood, urine, and meconium 20 hours after birth, high concentrations of buprenorphine and its metabolite norbuprenorphine were detected, with a higher buprenorphine/norbuprenorphine ratio than in adults, possibly as a consequence of immature hepatic function; no illicit drugs were found. The child had a weak withdrawal syndrome on the second day of life and recovered rapidly. The measured buprenorphine daily dose ingested by the newborn through mother's milk was very low (3.28 micrograms) and probably had little pharmacologic effect because no withdrawal signs could be noted when maternal feeding was later abruptly interrupted. Further investigations are required to determine whether buprenorphine can be considered to be a good alternative to methadone in the treatment of pregnant heroin addicts to prevent marked withdrawal syndromes in newborns.

Adult↗
PubMed1997

Trypanocidal effect of Ir-(COD)-pentamidine tetraphenylborate on Trypanosoma brucei and T. b. gambiense rodent models and serum kinetics in sheep.

Pentamidine di-(iridium cyclo-octadiene)tetraphenylborate, called Ir-(COD)-pentamidine tetraphenylborate, was selected from a primary screening as a promising trypanocidal compound. The compound was evaluated against three isolates: Trypanosoma brucei brucei CMP, T.b. brucei GVR 35 and T.b. gambiense Feo. On the T.b. brucei GVR 35 murine CNS model, no mouse was cured when the treatment was commenced 21 days post-infection whatever the treatment regimen. Nevertheless, in vitro the compound killed the trypomastigote forms of T. b. gambiense Feo at 0.6 microM. In vivo, the compound cured all mice infected 1 hour previously with T. b. gambiense Feo after a 10 mg/kg (6.3 mumol/kg) treatment subcutaneously administered in a single dose. Moreover, the compound was active at 1 mg/kg (0.6 mumol/kg) in a single dose against the early stage of the T. b. brucei Antat 1-9 sheep model. Serum kinetics data showed that pentamidine di-(iridium cyclo-octadiene) tetraphenylborate was distributed within deep compartment according to a monocompartmental model. The maximum iridium serum concentration was 198 micrograms/l corresponding to 1 mumol/kg of iridium derivative and this value remained stable for 30-50 hours post-treatment. Iridium was completely eliminated from the serum 700 hours post-treatment. all data obtained from these models are in favour of an activity in the early stage of the disease but indicate that the compound could not cross the blood-brain barrier despite its lipophilicity. Although iterative treatments with the compound rapidly induced the selection of iridium derivative refractory populations, the compound could be studied on pentamidine refractory strains.

Animals↗
PubMed1997

Simultaneous determination of lidocaine and bupivacaine in human plasma: application to pharmacokinetics.

High-performance liquid chromatography has been applied to the simultaneous determination of lidocaine and bupivacaine levels in human plasma, using etidocaine as internal standard. The method was found to be linear in the range 10-2,000 micrograms/l for lidocaine and 20-1,000 micrograms/l for bupivacaine. Within-day and day-to-day coefficients of variation were generally lower than 12%. The method was applied to a pharmacokinetic study of lidocaine and bupivacaine during peribulbar anesthesia in ocular surgery. Both compounds displayed a slow apparent elimination rate. The method described here permitted the determination of the complete pharmacokinetic profiles of the two anesthetics, although they were administered at quite different doses.

Aged↗
PubMed1997

Population pharmacokinetics of amikacin in geriatric patients studied with the NPEM-2 algorithm.

The population pharmacokinetics of amikacin were studied in 40 geriatric medicine patients (aged 59-95 years, average 78 years) by the NPEM-2 algorithm, using a 2-compartment model. The fitted parameters were: renal clearance of amikacin, expressed as a fraction of creatinine clearance (CLS) and volume of the central compartment, expressed as a fraction of body weight (VS). The nonrenal clearance of amikacin (CLi) and the transfer constants between the 2 compartments (k12 and k21) were held constant. The distribution of each pharmacokinetic parameter was characterized by the median and the 50% dispersion factor (DF50) which is the interval between the 25th and 75th percentiles, divided by 1.32. The parameters were thus estimated by the following values: CLs = 0.91 +/- 0.45 and Vs = 0.29 +/- 0.10 l x kg-1. The volume of distribution was increased with respect to the usual value of 0.20 l x kg-1. The interindividual variability was high, particularly for clearance. Although the median value of CLs was close to unity, indicating that for most patients the elimination kinetics of amikacin followed that of creatinine, there was a slight probability to observe much higher values of CLs (up to 5), indicating that for some aged patients the elimination of amikacin was less altered than that of creatinine. These parameters were used as reference population values to estimate the pharmacokinetics of amikacin in a second group of 20 patients by the Bayesian method, with 2 blood samples per patient. For each patient the fitted parameters were able to predict the plasma concentrations of amikacin during the next 72 hours with no significant bias and a precision of 3.5 mg x 1(-1). This study confirms the ability of the NPEM-2 algorithm to provide reference population values for use in Bayesian monitoring of aminoglycoside therapy.

Aged↗
PubMed1997

Tungsten determination in biological fluids, hair and nails by plasma emission spectrometry in a case of severe acute intoxication in man.

A healthy 19-year-old recruit in a French artillery regiment drank 250 mL of a mixture of beer and wine that had rinsed in a hot 155-mm gun-barrel. Fifteen minutes later, he complained of nausea followed by seizures. He was comatose for 24 h, presenting signs of encephalopathy. A moderate renal failure was noted initially and worsened to an extensive tubular necrosis with anuria on the day after the incident. The first toxicological investigations only showed a 0.31 g/L blood ethanol. Then inductively-coupled plasma (ICP) emission-spectrometry revealed very high concentrations of tungsten in the "beverage" as well as in gastric content, blood and urine (1540 mg/L, 8 mg/L, 5 mg/L, and 101 mg/L, respectively). The nature of the metal was confirmed by ICP coupled to mass spectrometry. A simple and reliable ICP quantitative assay of tungsten in biological fluids, hair and nails was then developed. It showed high blood levels (> 0.005 mg/L) until day 13 in spite of six hemodialyses, and in urine until D33. Tungsten was also incorporated in hair and nails. To the best of our knowledge, such an intoxication has never been reported before though this drinking seems to be traditional in the French Artillery. It has probably been favored by the unusually high volume of beverage absorbed and by the new alloy of the gun, containing tungsten. The clinical evolution was satisfactory over weeks and the patient was declared totally cured after five months.

Adult↗