Zeng-Pei Sun's research while affiliated with National Institute for the Control of Pharmaceutical and Biological Products and other places

From the definitions of retention time (tR) and resolution (Rs) in conventional chromatography, two fundamental equations for the retention behaviour and resolution of neutral solutes are derived and proved to be valid in all cases of micellar electrokinetic capillary chromatography (MECC). Two parameters, phase velocity ratio (Pr) and column availability (Aco), are introduced to reveal clearly the relationships and differences between MECC and conventional chromatography. The tR and Rs values may be either positive or negative in MECC. A negative tR indicates that the solute migrates toward the positive electrode and a positive tR toward the negative electrode. Rs > 0 means that the solute with a smaller value of the capacity factor (k') in the pair of solutes reaches the detector first, while Rs < 0 means that the elution order is the opposite. MECC can be classified into eight cases depending on the values of Pr for convenience of discussion. So far, MECC was usually performed in case IV and the resolution was poorer than that in conventional chromatography for given values of theoretical plate number, selectivity and k'. However, a better resolution can be obtained in cases II, VI and VIII when Pr < (1-k')/2. Cases VI, VIII and II are preferable to case IV for high resolution and should be more frequently employed in the future.

The effects of tetraalkylammonium salts and sodium dodecyl sulphate on the migration behaviour of human urinary components and other negatively charged or neutral solutes were investigated. The sulphate acted mainly on hydrophobic and positively charged substances, whereas the ammonium salts acted mainly on negatively charged solutes. By choosing the components of the eluent carefully, the free and conjugate forms of 3-methylflavone-8-carboxylic acid (MFA) in human urine, the major metabolites of flavoxate, could be simultaneously determined without pretreatment, using fenprofen as an internal standard. The calibration curve of MFA was linear in the range 1-50 micrograms/ml and the detection limit was 0.2 microgram/ml, which covered the urine levels encountered in pharmacokinetic studies. The intra-day and inter-day precisions of the method, expressed as the relative standard deviation, were less than 2 and 3%, respectively. This method was successfully applied to an excretion study of MFA in eight healthy volunteers, and the results were in agreement with data in the literature obtained by gas chromatography.

The capillary zone electrophoresis of tetracycline and its degradation products is described. Various substances, including surfactants and metal ions, were employed as additives in the running electrolyte to improve the resolution. Using disodium ethylenediaminetetraacetate as an additive in phosphate buffer solution, tetracycline and its degradation products were completely separated from each other. The baseline separation obtained completely meets the needs for determining the contents of tetracycline, 4-epitetracycline, anhydrotetracycline (ATC) and 4-epianhydrotetracycline (EATC) in tetracycline samples. Further, two unknown substances co-existing with ATC and EATC were separated that had not been mentioned or separated before. Further investigations using other techniques are needed to determine the structures of these two unknown substances. The pH dependence of the migration behaviour of tetracycline and its degradation products was also explored. The migration behaviour of zwitterionic substances is so depending on the pH of the buffer than the elution order may be changed with change in pH. The pH dependence of electroosmotic flow over the pH range 4–11 was also determined.

The separation and determination of seven sulphonamides and trimethoprim by micellar electrokinetic capillary chromatography were successfully achieved, employing sodium dodecyl sulphate (SDS) as a micellar phase and tetrabutylammonium bromide as additive. The effects of surfactant and modifier concentrations, pH and applied voltage on the retention behaviour of the solutes and the column efficiency were studied. The migration time of sulponamides increase with increasing SDS concentration and decreasing the applied voltage, but varies only slightly with pH. There is an optimum applied voltage at which a higher theoretical plate number is achieved, in contrast to the sulphonamides, the retention behaviour of trimethoprim gave a more obvious response to changes in the experimental conditions. The determination of three active ingredients in tablets was performed using sulphathiazole as an internal standard with good results. The theoretical plate number ranged between 2.0 x 10(5) and 2.8 x 10(5) with a 50-cm capillary.