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H Jaeger

Publications and source records attributed to H Jaeger.

At least 55 records · Page 3Linked to original sources
PubMed1988

High-performance liquid chromatographic determination of trans-doxepin and desmethyldoxepin.

An improved high performance liquid chromatographic (HPLC) assay for the quantitative determination of trans-doxepin (I) and desmethyldoxepin (II) in body fluids is presented. This HPLC assay, employing a UV-detector and perazine (III) as an internal standard, provides a very sensitive and selective determination in the low ng/ml range. The lower limit of quantification was 0.426 ng/ml (I) and 0.50 ng/ml (II); respectively. The calibration curve was linear in the measured range of 0.426-34.08 ng/ml (I) and 0.50-40 ng/ml (II). In combination with the excellent precision and accuracy data (c.v. values typically lower than 5%) and a recovery exceeding 90% for both compounds, the method is well suited for quantitative determinations of plasma samples generated during clinical studies, eg. evaluating the pharmacokinetics and/or bioavailability/bioequivalence as well as evaluations of clinical response.

Antidepressive Agents, Tricyclic↗
PubMed1988

Triple stage quadrupole mass spectrometric determination of bromocriptine in human plasma with negative ion chemical ionization.

A new MS/MS assay for the quantitative determination of bromocriptine in body fluids is presented. The selective reagent gas in combination with the registration of selected, characteristic negative ions (SIM) after collision activated decomposition (CAD) in a Triple-Stage-Quaddrupole-mass spectrometer, provides an exceptional selective and sensitive assay in the low pg/ml range. The lower limit of detection was about 1 pg/ml (at optimal measuring conditions) and the calibration curve was linear in the range of 10-200 pg/ml. The coefficient of variation for the imprecision and inaccuracy data was typically below 10%; the recovery from plasma always exceeded 75%. The sample introduction to the mass spectrometer was done by a direct exposure probe (DEP). Thus, the method is well suited for the reliable, rapid processing of large sample numbers generated e.g. from clinical studies evaluating the pharmacokinetics and/or bioavailability/bioequivalence of different formulations or from drug monitoring/clinical response programs. The assay has been successfully approved in several clinical studies evaluating different bromocriptine preparations.

Biological Availability↗
PubMed1988

[Studies of the pharmacokinetics and bioavailability of a new trimethoprim/sulfamethoxazole preparation in healthy volunteers].

The objective of this study was to determine both the pharmacokinetic parameters and the bioavailability of a newly developed trimethoprim/sulfamethoxazole preparation (cotrimoxazole, Kepinol forte, 160 mg of trimethoprim/800 mg of sulfamethoxazole) in comparison with a reference preparation customary in trade and registered according to the AMG 1976, after single oral administration. For this purpose the test and the reference preparation were examined in a randomized 2-way crossover design (Latin square) in 12 volunteers each. Both dosage forms led to maximum plasma levels of approx. 1250 ng/ml of trimethoprim and about 40 micrograms/ml of sulfamethoxazole 1.5-2 h after application; the plasma half-lives were about 9 h for trimethoprim and around 8.5 h for sulfamethoxazole. The statistical comparison (ANOVA, confidence intervals according to Westlake, Pratt-Wilcoxon test) of the pharmacokinetic parameters found in the study resulted in bioequivalence of the newly developed trimethoprim/sulfamethoxazole preparation and the reference preparation. Furthermore, after the administration of both preparations no marked side effects worth mentioning were observed, suggesting a good and comparable clinical tolerability of the two preparations.

Adult↗
PubMed1988

[Postoperative treatment of phantom pain and causalgias with calcitonin].

Results of IV calcitonin treatment in patients suffering from postoperative phantom limb pain (n = 12) or causalgia following peripheral nerve lesions (n = 4) are reported. All patients were complained of severe pain after a traumatic event or amputation, with disturbed sleep in many cases. After only 1-2 infusions 10 patients with phantom limb pain (83%) were discharged from hospital pain-free. Pain was effectively reduced by up to 5 infusions in 2 patients (17%). A follow-up for maximally 24 months showed a recurrence of pain in only 4 patients with obvious stump problems or reamputations. Three patients with causalgia also profited from a remarkable but transitory pain reduction; in 1 patient therapy was ineffective. Recurrent pain due to causalgia could not be improved by repeated calcitonin infusion, although this was effective for phantom limb pain. The administration of calcitonin IV can be recommended as a valuable treatment for phantom limb pain and causalgias in the early postoperative period. Therapy was effective with negligible side-effects, and long-term follow-up revealed a long-lasting effect.

Arm↗
PubMed1988

Determination of flurazepam and its major metabolites N-1-hydroxyethyl- and N-1-desalkylflurazepam in plasma by capillary gas chromatography.

In the present paper we describe a method for the quantitative determination of flurazepam (I) and two of its metabolites, N-1-desalkylflurazepam (II) and N-1-hydroxyethylflurazepam (III), in serum after therapeutic dosings is described. The method is sensitive (lower limit of quantification for I and III: 1 ng/ml, for II: 2 ng/ml), selective and--compared to the analytical approaches already published--simple to handle. Thus this assay is well suitable for determinations during clinical studies (e.g. evaluating the pharmacokinetics, bioavailability/bioequivalence). Following simple extraction- and derivatization steps (the latter being only required for III) the extract is injected directly onto a fused-silica, bonded-phase capillary column of a gas chromatograph and the compounds of interest detected by an electron-capture detector (ECD). The assay has been used successfully during several clinical studies, especially as very low dosages result in also very low blood concentrations.

Chromatography, Gas↗
PubMed1988

Gas chromatographic/mass spectrometric determination of clonidine in body fluids. Application to pharmacokinetics.

Depending on the very low therapeutic doses of clonidine and the resulting low blood levels (in the pg/ml range), for quantitative determinations in body fluids only methods of necessary selectivity as well as corresponding sensitivity can be employed successfully. Furthermore, the method should also be suited for the rapid processing of large sample numbers generated e.g. during clinical studies evaluating pharmacokinetics and/or the bioavailability/bioequivalence. Thus a gas chromatographic/mass spectrometric assay was developed employing fused-silica, bonded-phase capillary columns, chemical ionization with ammonia as a selective reagent gas in combination with the registration of preselected, characteristic negative ions (SIR, NICI) and a deuterated internal standard. Therefore, the method proves to be exceptionally selective and sensitive: a lower limit of detection of 10 pg/ml plasma is reached, the calibration curve is linear in the 25-1500 pg/ml range and the recovery from blood exceeds 90%. The assay has been successfully approved in several clinical studies, whereby especially the simple sample preparation led to very short times for analysis.

Clonidine↗
PubMed1987

Quantification of tamoxifen and N-desmethyltamoxifen in human plasma by high-performance liquid chromatography, photochemical reaction and fluorescence detection, and its application to biopharmaceutic investigations.

The anticancer drug tamoxifen and its major metabolite N-desmethyltamoxifen are quantified in human plasma down to subnanogram amounts by high-performance liquid chromatography. Plasma is alkali-buffered and extracted with hexane. The organic solvent is evaporated and the residue dissolved in the mobile phase. An aliquot is sampled automatically and chromatographed. The analytes are detected after postcolumn UV irradiation and rearrangement to substituted phenanthrenes by their intense fluorescence. Precise handling of exact volumes facilitates external calibration. Statistical data for precision and accuracy are given and illustrate reliable quantification. The method is applied to the samples of a clinical study, and the pharmacokinetic parameters of both analytes are presented. The novel design of the photochemical reactor is discussed, with respect to peak broadening and photochemical recovery. The measured peak broadening is smaller than theoretically predicted, owing to non-helical coiling.

Biopharmaceutics↗
PubMed1987

Determination of nitrates in plasma.

Because of the high efficacy of existing nitrates, alternative dosage formulations have been developed rather than new compounds. These new formulations challenge the analyst to develop analytical methods with lower sensitivity and higher precision. Isosorbide dinitrate is analysed in the presence of its major metabolites isosorbide 2-mononitrate and isosorbide 5-mononitrate. The present method is an improvement over previously published methods. It is not possible to analyse glyceryl trinitrate and its major metabolites 1,2-glyceryl dinitrate and 1,3-glyceryl dinitrate with the necessary sensitivity in one chromatogram. A 2-step procedure is therefore applied. The extraction procedures, the gas chromatographic conditions, imprecision and inaccuracy of the methods, the lower limits of quantitation, sample chromatograms and applications of all methods are described in detail. Thus, the possibilities of modern analytical methods in the determination of nitrates in the lower picogram region are demonstrated.

Biotransformation↗
PubMed1987

[Biotransformation and bioequivalence of a new nifedipine preparation].

Following a single dose of two 5 mg soft gelatine capsules with nifedipine (Pidilat as a test preparation and a commercially available reference preparation) to 12 healthy volunteers in a randomized, 2-fold cross-over trial (latin square), blood samples were drawn up to 16 h post application (p.a.). The nifedipine plasma levels were quantitatively determined by a capillary gas chromatographic assay. Some important pharmacokinetic parameters as well as the bioavailability/bioequivalence were evaluated and subsequently compared for possible statistically significant differences between the preparations. Approximately 0.5 h p.a. mean peak plasma concentrations of about 110-120 ng/ml were reached; the mean terminal half-live was 1.5 h. The plasma level-time curves were-except for the negligible different peak concentrations-virtually identical; thus both preparations are considered to be bioequivalent.

Adult↗
PubMed1987

Determination of methyldopa in plasma using high-performance liquid chromatography with electrochemical detection. Application to pharmacokinetic/bioavailability studies.

The problem of quantitatively measuring methyldopa (a-methyldopa) in biological matrices after applying therapeutic doses to humans is still challenging. Numerous methods have been published but most of them require a tedious, time-consuming sample preparation, are not specific enough or lack the necessary sensitivity. As the basis of conclusive human pharmacokinetic and bioavailability/bioequivalence studies is a validated analytical method, which is reliable, selective, sensitive and able to proceed hundreds or even thousands of samples in a limited time, an assay to fulfill these needs was developed. The present method employs a hiph-performance liquid chromatographic system consisting of a pump, an ODS column, an autosampler and an electrochemical detector. The assay is sensitive down to 50 ng/ml plasma, the calibration curves are linear in a range of 50-2000 ng/ml, the chromatographic peaks are well resolved and the precision and accuracy are excellent. The assay has been successfully used for the determination of very low methyldopa plasma levels during several clinical studies.

Biological Availability↗
PubMed1987

Gas chromatographic--mass spectrometric determination of haloperidol in plasma. Application to pharmacokinetics.

An improved gas chromatographic-mass spectrometric chemical ionization assay for the quantitative determination of haloperidol in body fluids is presented. A fused silica, bonded phase capillary column, combined with negative ion chemical ionization (NICI), ammonia as a selective reagent gas and the monitoring of preselected characteristic ions (SIM), provide the combined sensitivity and selectivity necessary for reliable measurements in the low ng/ml range. The lower limit of detection was 0.1 ng/ml plasma and the calibration curve linear in the measured range of 0.1-5 ng/ml. In combination with the excellent imprecision and inaccuracy data and a recovery exceeding 90%, the method is very well suited for quantitative determinations of plasma samples generated during clinical studies, e.g. evaluating the pharmacokinetics and/or bioavailability/bioequivalence of haloperidol.

Biological Availability↗
PubMed1986

Relative bioavailability of two spray formulations of nitroglycerin.

Twelve healthy male volunteers received two sublingual doses of 0.4-mg nitroglycerin from two metered-dose spray products, A and B. Plasma samples were collected immediately before and for up to 6 h following each dose. The samples were immediately extracted and analyzed for nitroglycerin. The results show striking differences between the two formulations. The mean AUC for preparation A, 159 +/- 66 h X pg/mL, was 2.7 times greater than for B, 59 +/- 33 h X pg/mL. The mean maximum plasma concentration for A was 1387 +/- 620 pg/mL which was 4.1 times greater than the mean maximum plasma concentration for preparation B (340 +/- 234 pg/mL). The time of maximum plasma concentration also occurred earlier for preparation A versus B, 4.3 +/- 1.6 versus 8.3 +/- 2.0 min, respectively. Such bioavailability differences may indicate therapeutic advantages for preparation A.

Aerosols↗
PubMed1986

Pharmacokinetics of ergotamine in healthy volunteers following oral and rectal dosing.

Twenty-four healthy volunteers participated in a study on the disposition of ergotamine following oral and rectal administration. Plasma samples were collected surrounding each dose of medication and a new mass spectrometry method was used for quantitation of the samples. A mean peak plasma concentration of 454 pg/ml was measured an average of 50 min following a 2 mg rectal dose. In contrast, the 2 mg oral dose produced a mean peak plasma concentration of 21 pg/ml an average of 69 min following the dose. Area under the concentration time curve indicated a relative bioavailability of 5% for the oral dosage form. Conflicting data on ergotamine disposition highlight the factors which may be responsible for determining bioavailability and pharmacologic activities of the compound.

Administration, Oral↗
PubMed1986

[The pharmacokinetics and bioavailability of urapidil. In vitro/in vivo correlations of different experimental formulations].

The pharmacokinetic parameters, including the relative bioavailabilities of two experimental batches of a 60-mg urapidil slow release-capsule and a 30-mg urapidil drinking ampoule (Ebrantil) had to be evaluated in a randomized, three-period change-over study with 12 healthy volunteers after single dosing. The appropriate parameters for the capsule formulations were compared with their dissolution rates obtained by different in vitro models. The capsules showed different half-change, but comparable single-fluid dissolution profiles. Both batches of the capsules showed equivalence with respect to the extent of absorption, in connection with 100% relative bioavailability on average. A correlation of the in vivo parameters Tmax and Cmax with the half-change model can be assumed.

Adult↗
PubMed1986

Pharmacokinetics and bioavailability of three different galenic nifedipine preparations.

In a randomized three-way crossover study with twelve volunteers the bioavailability and main pharmacokinetic parameters of three different galenic formulations of nifedipine (hard gelatine capsule with pellets = preparation A, soft gelatine capsule with liquid nifedipine = preparation B, retard-tablet = preparation C) were determined. Plasma concentrations of nifedipine were measured by capillary gas-liquid chromatography up to 24 h after single dosing as well as up to 48 h after multiple doses of the drugs (steady state). Statistically significant differences between the preparations were found for AUC, Cmax, and Tmax. In all respects preparation A was intermediate to the other preparations. Plasma levels of 40 ng/ml or more were reached for most subjects within the first half hour after application of a single dose of preparation A and under steady state conditions plasma concentrations of 25 ng/ml or more could be upheld with this preparation for a longer time than with the reference retard tablet (preparation C). No accumulation of nifedipine in plasma occurred following multiple dosing.

Adult↗