Updating the European Pharmacopoeia impurity profiling method for terazosin and suggesting alternative columns.

This work was motivated by the demand of European Directorate for the Quality of Medicines and HealthCare (EDQM). A new liquid chromatographic (LC) method was developed for terazosin impurity profiling to replace the old European Pharmacopoeia (Ph. Eur.) method. This new method is published as part of the new Ph. Eur. monograph proposal of terazosin in Pharmeuropa issue 32.2. The aim of the method renewal was to cut the analysis time from 90 min (2 × 45 min) down to below 20 min. The Ph. Eur. monograph method is based on two different chromatographic separations to analyze the specified impurities of terazosin. The reason for the two methods is that two of the impurities are not sufficiently retained in reversed phase (RP) conditions, not even with 100% water as eluent. Therefore, next to RP, an ion-pair (IP) chromatographic method has to be applied to analyze those two impurities. With our new proposed method it was possible to appropriately increase the retention of the two critical compounds using alternative stationary phases (instead of a C18 phase which is suggested by the Ph. Eur. method). Applying a pentafluoro-phenyl (PFP) stationary phase, it was feasible to separate and adequately retain all the impurities. The detection wavelength was also changed compared to the Ph. Eur. method and is now appropriate for the detection and quantification of all impurities using perchloric acid in the mobile phase at low pH. Another goal of the present study was to develop a generic workflow and to evaluate the chromatographic resolution in a wide range of method variables and suggest some replacement columns for terazosin impurity profiling. Retention modeling was applied to study the chromatographic behavior of the compounds of interest and visualize resolution for the different columns, where a given criterion is fulfilled. A zone (set of chromatographic conditions) of a robust space could be then quickly identified by the overlay of the individual response surfaces (resolution maps). It was also demonstrated that two columns from different providers (Kinetex F5 and SpeedCore PFP) can be used as replacement columns, providing sufficient resolution at the same working point and a high degree of robustness.

Symptomatic comparison in efficacy on patients with benign prostatic hyperplasia treated with two therapeutic approaches.

OBJECTIVES: A randomised controlled trial was performed to compare the symptomatic effects on patients with benign prostatic hyperplasia (BPH) treated by two therapeutic approaches - the Western medicine (WM) and traditional Chinese medicine (TCM). METHODS: Four primary outcome measures, namely the quality of life (QOL), maximum urine flow ratio (UFR), International Prostate Symptom Score (IPSS) and prostate volumes, as well as four urethra-related and 35 non-urethra-related symptoms, were investigated to evaluate the effects on 31 BPH patients subjected to WM (Terazosin Hydrochloride Hytrin, THH) and 30 cases to TCM (herbal Saxifrage tablet, HST). The effects of both treatments are compared by the two-sample Kolmogorov-Smirnov test. The contributions of symptoms for four assessments are analysed by the logistic regression model and the Chow test. RESULTS: The effect of TCM is weaker than that of WM in the assessment of the IPSS score (p<0.05), and both treatments are similar in the prostate volumes, the maximum UFR and the QOL assessments (p>0.05), as well as in the effective number of urethra-related or non-urethra-related symptoms before and after treatment (p>0.05). By comparing the linear regression models, different urethra-related and non-urethra-related symptom patterns associated with TCM and WM therapies are detected for four assessments, especially for the prostate volume assessment (p<0.01). CONCLUSION: TCM (HST) is a potentially effective treatment in improving the QOL, prostate volumes and maximum UFR for patients with BPH, though it is less effective in ameliorating the IPSS score when compared with WM (THH). The non-urethra-related symptoms experienced by BPH patients might be one of the parameters to further achieve the tailored diagnosis and treatment for BPH.

A rapid and simple high-performance liquid chromatography method for the determination of human plasma levofloxacin concentration and its application to bioequivalence studies.

A high-performance liquid chromatography method with fluorescence detection (HPLC-FLD) for the determination of levofloxacin in human plasma is described. Neutralized with phosphate buffer (pH 7.0), the sample (0.1 mL) was extracted with dichlormethane (1 mL). After voltex-mixing and centrifuged at 3000g for 6 min at 4 degrees C, the upper aqueous layer was aspirated using a micro vacuum pump and the organic layer was directly transferred to a clean test tube without pipetting. The organic solvent was evaporated and the residues were reconstituted with the mobile phase. Levofloxacin and terazosin (internal standard, IS) were chromatographically separated on a C(18) column with a mobile phase containing phosphate buffer (pH 3.0, 10 mm), acetonitrile and triethylamine (76:24:0.076, v/v/v) at a flow rate of 1 mL/min. The analytes were detected using fluorescence detection at an excitation and emission wavelength of 295 and 440 nm, respectively. The linear range of the calibration curves was 0.0521-5.213 microg/mL for levofloxacin with a lower limit of quantitation (0.0521 microg/mL). The retention times of levofloxacin and terazosin were 2.5 and 3.1 min, respectively. Within- and between-run precision was less than 12 and 11%, respectively. Accuracy ranged from -6.3 to 4.5%. The recovery ranged from 86 to 89% at the concentrations of 0.0521, 0.5213 and 5.213 microg/mL. The present HPLC-FLD method is sensitive, efficient and reliable. The method described herein has been successfully used for the pharmacokinetic and bioequivalence studies of a levofloxacin formulation product after oral administration to healthy Chinese volunteers.

Sensitive fluorimetric method based on sequential injection analysis technique used for dissolution studies and quality control of prazosin hydrochloride in tablets.

This report introduces a fully automated flow system for drug-dissolution studies based on the coupling of the sequential injection analysis (SIA) technique with a conventional dissolution apparatus. The methodology described was used for monitoring of dissolution profiles of prazosin hydrochloride (PRH) in pharmaceutical formulation. The very sensitive fluorimetric detection of PRH was performed at lambda(ex)=244 nm (lambda(em)>or=389 nm). Under the optimal conditions, the calibration curve was linear over the range 0.02-2.43 mg x l(-1) of PRH with R.S.D. 1.89, 1.23, and 1.80% (n=10) when determining 0.02, 1.22, and 2.43 mg x l(-1) of PRH in standard solutions, respectively. Equation of the calibration curve was calculated giving the following values: F=4.108 c-3.9 (n=6), r=0.9996. Detection limit was calculated 0.007 mg x l(-1) of PRH. The dissolution test of Deprazolin tablets was programmed for 60 min, with a continuous sampling rate of 70 h(-1) under conditions required by USP 26. Results obtained by SIA technique compared well with HPLC standard method.