Comparative bioanalytical study of3H-deramciclane in dog plasma, using a gas chromatography-nitrogen-selective detection (GC-NPD), a new GC-radiochemical detection (GC-RD) and a liquid scintillation method

Summary A new, highly sensitive and selective gas chromatography method, using radiochemical detection (GC-DR) was developed for the selective determination of³H-labelled deramciclane and its N-desmethyl metabolite in dog plasma. Inter-day accuracy and precision, as well as system suitability of the GC-RD method was investigated during the method validation. The calibration curve was proved to be linear (r=0.9986) in a wide concentration range (13–1000 ngeqv mL⁻¹) The lower limit of quantitation (LLOQ) was 13.7 ngeqv mL⁻¹, and the limit of the detection (LOD) was 1 ngeqv mL⁻¹. Using this new GC-RD method, plasma levels of³H-labelled deramciclane and its metabolite were determined in dogs, after the administration of a single 10 mg kg⁻¹ oral dose. Pharmacokinetic curves and the calculated pharmacokinetic parameters were compared to those obtained using a previously elaborated gas chromatography-nitrogen selective detection method (GC-NPD) and to those obtained by measuring the plasma level of total radioactivity (liquid scintillation counting, LSC). Pharmacokinetic curves and the calculated pharmacokinetic parameters obtained with the two different gas chromatography detection methods (NPD and RD) showed good correlation. Comparison of these results to those acquired by total radioactivity measurement demonstrated that deramciclane was intensively metabolised. Moreover, the biological half-life (t ₁ ^2/β ) of the unknown metabolites proved to be more than a magnitude longer than the half-life of the parent compound or that of N-desmethyl metabolite. Presented at: Balaton Symposium on High-Performance Separation Methods, Siófok, Hungary, September 3–5, 1997.     

Comparison of the fragility index of different eudragit polymers determined by activation enthalpies

The present study aimed to apply fragility index (m) of polymers in the determination of the optimal amount of plasticizer in polymer films. The fragility index of different Eudragit polymers (RS, RL, EPO) was assessed by differential scanning calorimerty (DSC), applying the Arrhenius connection (logq–1/T _g). The fragility of Eudragit EPO films proved to be the highest, while in the case of RS and RL, the increase of the alkyl-chain length caused the increase of fragility. Studying the effect of plasticizer (triethyl citrate, TEC) on the m value of Eudragit RL and RS films, a near linear reduction of the fragility index could be observed between 5–30% TEC concentration, but above 30%, this value leveled out to constant.     

Evaluation of a New LC Method for Analysis of Vancomycin Released from an Orthopaedic Drug Carrier System

Because of the increasing spread of antibiotic multiresistance, the drug vancomycin is a commonly used in orthopaedic surgery. The objective of our research was to develop a new method for analysis of the drug carrier systems—i.e. systems providing prolonged drug release—used in orthopaedics. The development of a pharmaceutical formulation requires a simple method for analysis of the active ingredient. For characterization of a drug release profile as a function of time, release of antibiotics from hydrophobic matrices was followed by in vitro tests. A rapid LC method, using a 2.1 mm × 150 mm, 5 μm particle, C₁₈ column and methanol–water–acetate buffer as mobile phase was developed for quantitative analysis of samples taken in drug release studies.

     

LC-UV Assay of Tolperisone HCl from Sustained Release Matrix Tablets

Tolperisone HCl is a central muscle relaxant, which was incorporated in a matrix system formulated with poly(ethylene oxide)–PEO, in order to achieve adequate gastric residence time. This tablet presents considerable analytical difficulties in the quantitative determination of the drug, because the PEO matrix causes significant increase of viscosity in the samples. Our purpose was to develop a reproducible sample preparation method, which is adapted from parameters of the in vitro dissolution test and validate an LC-UV analytical method, which allows good recovery of the drug (99.97%). The developed analytical method was suitable for quantitative analysis of tolperisone HCl in matrix tablets.     

OPLC Comparison of Methods for Aqueous Extraction of Sennae folium and Tiliae flos Plant Samples

JPC – Journal of Planar Chromatography – Modern TLC - A new, simplified open-vessel microwave extraction (OVME) method has been used to prepare aqueous extracts of Sennae folium and...     

Fully On-Line Hyphenation of an Experimental OPLC Separation Unit with Diode-Array Detection and Mass-Spectrometry (OPLC-DAD-MS) for Analysis of Xanthine Compounds

JPC – Journal of Planar Chromatography – Modern TLC - The newly developed experimental OPLC separation unit 100 (OSU 100) has been used for fully on-line multiple hyphenation using the...     

Metabolite analysis,isolation and purity assessment using various liquid chromatographic techniques combined with radioactivity detection

During the discovery of metabolic routes of a drug candidate, radioactively labeled substances are administered. This study reports the multidimensional application of overpressured layer chromatography (OPLC) and high-performance liquid chromatography (HPLC) coupled with online or off-line nondestructive radioactivity detection methods in metabolism studies. Among these methods, digital autoradiography and flow-cell radioactivity detectors (RD) using solid scintillators are used. In this study, the hyphenation of OPLC with RD is reported. The application of the OPLC-RD technique is demonstrated on a metabolism study as well as the multidimensional chromatographic selectivity using normal-phase OPLC for the separation in the first dimension, followed by reversed-phase HPLC-RD, which provides additional selectivity to the separation. Information regarding the identity of radiolabeled metabolites and data obtained from spectroscopic methods could be advantageously used during structure elucidation.     

Determination of nifedipine in human plasma by high performance liquid chromatography using column-switching technique

A highly sensitive reversed-phase HPLC method has been developed for the determination of nifedipine in human plasma with electrochemical detection. A liquid-liquid extraction procedure is used in sample preparation with an average extraction recovery of 75%. Removing the highly lipophilic plasma components using a special column switching technique reduced the duration of the HPLC measurement from 30 to 9 min. The method is applicable for the pharmacokinetic characterization and bioavailability study of a sustained-release (retard) formulation of nifedipine and for human drug monitoring as it is indicated by the validation of the analysis method. The assay gave a linear response over the concentration range 2.5–50 ng/ml. All the validation parameters are within the internationally required limits.     

Determination of ambroxol in dog plasma by high-performance liquid chromatography and UV detection

Summary A new sensitive HPLC-UV method has been developed and validated for the determination of amboroxol in dog plasma enabling the investigation of a newly developed 75 mg ambroxol-containing retard capsule of EGIS Pharmaceuticals Ltd., Budapest, Hungary. A gradient method was used for removing the longer retained plasma components of no interest. The separation was performed on a BDS Hypersil C18 (5 μm, 250×2.1 mm) analytical column, supplied with a 10 mm guard column containing the same packing material. The detection was performed at 210 nm. The calibration curve was linear in the range 25–2000 ng·mL⁻¹. Nerisopam (EGIS-6775) was used as internal standard. Presented at Balaton Symposium on High Performance Separation Methods, Siófok, Hungary, September 1–3, 1999     

Determination of acyclovir in dog plasma by HPLC using a column switching technique

Summary A new HPLC-UV method has been developed and validated for the pharmacokinetic linearity study of Telviran^? tablets containing 200, 400, and 800 mg acyclovir. RP-18 solid phase extraction has been developed for sample preparation. Guanosine (9-[β-D-ribofuranosyl]-guanine) was used as internal standard. The separation was carried out on an ODS Hypersil (5 μm, 200×4.5 mm) analytical column, supplied with a 20 mm guard column containing the same packing material. A column switching technique was applied for the elimination of the endogenous compounds eluting with longer retention times than the investigated compounds, so the analysis time was considerably shorter compared with the time of gradient elution. The eluent was 0.5% triethylamine in water, the pH was adjusted with orthophosphoric acid (85%) to pH5. The detection was performed at 254 nm. The calibration curve was linear in the concentration range 10–5000 ng mL⁻¹. The new bioanalytical method was successfully applied for a pharmacokinetic linearity study in dogs. Presented at Balaton Symposium on High Performance Separation Methods, Siófok, Hungary, September 1–3, 1999