Pharmacokinetics and tissue distribution of a bioactive sesquiterpenoid from Polygonum jucundum following oral and intravenous administrations to rats.

Polygonum jucundum is a traditional Chinese medicine used for the treatment of diseases. The major bioactive compound in the ethanol extract of P. jucundum is 2α-hydroxyl-3ß-angeloylcinnamolide (HAC), a drimane-type sesquiterpenoid, which possesses anti-inflammatory activities. The purpose of this study was to investigate in vivo pharmacokinetics and tissue distribution of HAC after oral and intravenous administrations to rats by using a reversed-phase high performance liquid chromatography in conjunction with mass spectrometry (LC-MS). Chromatographic separation was achieved on a C18 column within 8 min. Quality control samples for both tissues and plasma demonstrated accuracy and precision within 94.59-107.74% of the nominal values and 1.65-10.77% relative standard derivative (RSD), respectively. The pharmacokinetic profiles, estimated by using non-compartment models, revealed that HAC was rapidly absorbed into the systemic circulation and was widely distributed throughout the body, followed by a rapid elimination phase. The highest amount of HAC was found in kidney, followed in order by lung, heart, spleen and liver. The current paper was the first report on the pharmacokinetic profiles of HAC in rat plasma and tissues after oral and intravenous administrations. It could provide a meaningful insight for the clinical applications of this bioactive compound extracted from the traditional Chinese medicine.

Development of a two-step tier-2 dissolution method for blinded overencapsulated erlotinib tablets using UV fiber optic detection.

Measuring dissolution of a comparator drug overencapsulated in a hard gelatin shell is necessary when determining performance of the native and blinded formulations. However, the gelatin in the shell may form cross-links upon storage at stressed conditions, resulting in slow dissolution of the encapsulated drug. The aim of this study was to develop a dissolution approach for a hard-gelatin overencapsulated formulation of a comparator drug, erlotinib, which can overcome cross linking of the capsule shell. In this case, following the USP two-tier dissolution test by simply adding an enzyme did not dissolve the cross-linked capsules because the medium used in the method for erlotinib described in the FDA Dissolution Database contains sodium dodecyl sulfate that inhibits the activity of the enzyme. Changing the method by using different surfactants was not considered acceptable because it is preferable to closely follow the compendial method for the comparator. A two-step tier-2 method was developed as a solution, without significant change to the compendial method conditions. It uses 0.1N HCl + pepsin as the initial medium to help capsule break-up. SDS is added at 15 min after the testing starts to ensure dissolution of the drug. This may be a useful general approach for dealing with cross-linking in over-encapsulated comparators. A UV fiber optic spectrophotometer was used for in situ, real-time detection of the dissolution profile during method development studies. The fast sampling rate available with this type of detection was important in elucidating the events occurring during dissolution and determining the optimal time of the SDS addition.

Impact of column temperature and mobile phase components on selectivity of hydrophilic interaction chromatography (HILIC).

The retention mechanism and chromatographic behavior for different polar analytes under hydrophilic interaction chromatography (HILIC) conditions have been studied by application of different mobile phases and stationary phases to various analytes at different temperatures. In addition to the commonly accepted mechanism of analyte liquid-liquid partitioning between mobile phase and water-enriched solvent layer which is partially immobilized onto the surface of the stationary phase, hydrogen-bonding, hydrophobic interaction, and ion-exchange interactions may also be involved. The predominant retention mechanism in HILIC separation is not always easily predictable. It can depend not only on the characteristics of the analytes but also on the selection of mobile and stationary phase compositions. The objective of this review is to evaluate the potential application of column temperature and mobile phase composition toward improving HILIC selectivity. The functional groups from analyte structures, stationary phase materials and organic mobile phase solvents will be highlighted.

Separation of amino acids, peptides and corresponding Amadori compounds on a silica column at elevated temperature.

Maillard reaction of glucose with amino acids and peptides has become a very important experimental model in the food flavor and pharmaceutical industries for better understanding the mechanism of food flavor generation and drug stability. Because of the amino acid and sugar functional groups present in their structures, most of the reaction components formed during the initial stages of Maillard reaction as well as the substrates are relatively polar. These compounds are poorly retained on a conventional reversed phase column. While polar stationary phases like HILIC column do provide better retention for these polar components, method selectivity could still be a challenge due to the structural similarity between these analytes. In this report, parameters such as pH, mobile phase composition and temperature were investigated using different brands of bare silica columns in order to separate glycine (G), diglycine (DG), triglycine (TG), and the corresponding Amadori compounds of glucose-glycine (GG), glucose-diglycine (GDG) and glucose-triglycine (GTG). An excellent separation for glycine, glycine peptides and their Amadori compounds was obtained on a bare silica column at an elevated temperature.

Development and validation of HPLC methods for the determination of potential extractables from elastomeric stoppers in the presence of a complex surfactant vehicle used in the preparation of parenteral drug products.

HPLC methods were developed and validated for potential extractables [zinc dithiocarbamate, 2,6-di-tert-butyl-para-cresol (BHT), octylated diphenylamine antioxidant, sulfur, pentylphenol, and tetrakis(methylene(3,5-di-tert-butyl-4-hydroxyhydro cinnamate))methane] from commercial elastomeric stoppers in a complex surfactant matrix. These stoppers were proposed to be part of the container-closure system for experimental formulations containing the surfactant, polyoxyethylated Castor oil (USP/NF) (POE Castor oil) and ethanol. The presence of POE Castor oil in the formulation posed unique challenges to the development and validation of the HPLC methods. POE Castor oil, also known as Cremophor, is a viscous and complex solubilizing agent with a number of uncharacterized fractions. Hence the goal was to identify HPLC conditions that would be suitable for the separation, detection, and quantitation of the potential stopper extractables in the presence of such a complex drug product matrix. A number of experiments were performed to evaluate the effects of different columns, mobile phase composition, injection volume, and gradient profile on the separation and detection of the potential stopper extractables. The quantitation limits of these stopper extractables are between 1 and 10 ppm. The methods demonstrate good linearity, acceptable accuracy, and precision.