| Objective: 1.To establish a flame atomic absorption spectrophotometry method for the determination of potassium ion in human urine. 2. To study the pharmacokinetics and bioavailability of potassium chloride sustained-release tablets in healthy volunteers, and to evaluate its characteristics of absorption, distribution, elimination and excretion kinetics. To observe the possible influencing factors on the absorption, distribution and elimination of potassium ion and to provide evidence for its reasonable clinical applications.Methods: 1 .Urine samples were disposed and detected by flame atomic absorption spectrophotometry method. Lamp current was 4mA. Detection wavelength was 766.5nm. Band pass width was 0.5nm. Flame style was Air-C2H2. Flow rate of burning gas was 1.2L·min-1. Height of burner was 7.0mm. 2. 20 healthy male volunteers were divided into two groups randomly according to two period cross-over test design. Volunteers were orally given the test or reference preparation of potassium chloride tablets during the two periods. Each period of 5 days was divided into 3 stages: the 1st day for food balance, the next 2 days for baseline phase, and the last 2 days for drug administration. 3g potassium chloride tablets (equal to 39.85mg) were orally given to the volunteers at 7a.m. of the 4th day of every period. Urine samples were collected before and 0-1,1-2,2-4,4-6, 6-8, 8-10, 10-12,12-15,15-24h after administration. The volume of all the urine samples was recorded and 10ml were left and stored at -20℃before use. The second period experiment was carried out same as above method 1 week's later. The validated flame atomic absorption spectrophoto metry method was used to determine potassium chloride in urine samples. The pharmacokinetic parameters of potassium chloride were calculated and evaluated by software of DAS 2.0. Relative bioavailability was calculated according to the total excretion amount of potassium chloride. Analysis of variance, t-test and (1-2α) confidence interval were used to evaluate the bioequivalence of test and reference preparation.Results: 1.The linear range of the calibration curve for determination of potassium ion by flame atomic absorption spectrophotometry was 0.05-2mg·mL-1 with a correlation coefficient was 0.9994. The Absolute and relative recoveries were (80.3-85.3) % and (93.5-113.1) %, respectively. The intra- and inter-day RSD were less than 8.2% and 9.5%. Potassium ion was stable when storage at -20℃for seven days and after two freeze-thawing cycles. 2. The main pharmacokinetic parameters of test and reference preparation of potassium chloride sustained-release tablets were respectively as follows: t1/2 (3.566±1.695) h and (3.963±1.875) h, the maximum excretion amount, Amax (7.70±1.76)mmol and (7.11±2.20)mmol, Tmax (5.4±2.3)h and (4.3±3.0)h, the accumulation excretion amount of 24h after administration (28.52±5.22)mmol and (27.88±4.69)mmol. The relative bioavailability of potassium chloride test preparation was (103.6±20.1) %.Conclusions: 1. The developed method was rapid, simple, sensitive and accurate. It can be used to determine the concentration of potassium ion in human urine. 2. The relative bioavailability of potassium chloride test preparation in human was (103.6±20.1)%. 3. Analysis of multiple factor variance indicated that there was no significant difference between preparations and periods, but statistical difference was observed between individuals. The two preparations were bioequivalent between individuals, periods and preparations evaluated by further t-test and (1-2α) confidence interval analysis.
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