A rapid and sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method for quantification of sitagliptin in human plasma and urine had been developed. This method was applied to the pharmacokinetics study of sitagliptin tablet after single- and multiple-dosing in Chinese population. Plasma samples were prepared by a liquid-liquid extracted method, and urine samples were diluted. Compounds were analyzed by multiple reaction monitoring (MRM) mode with a electrospray ionization (ESI) interface. Mobile phase consisted of methanol and water (85 : 15, v/v). The linear concentration range of calibration curve was 0.5-1 000 ng.mL-1. and 0.2-100 µg.mL , intra-run/between-run accuracy was 98.98%-103.69% and 97.63%-102.29%, intra-run/between-run precision was <5.51% and 4.26% for plasma and urine sample, respectively. The stability of sitagliptin stock solution was tested for 55 days at -30 °C. Sitagliptin was stable when stored under the following conditions: 24 hours in the autosampler after sample preparation; 24 hours at room temperature, after 3 freeze and thaw cycles (from -30 °C to room temperature), 40 days at -30 °C for plasma and urine samples. The absolute recovery in plasma was 71.1%, and no matrix effect was founded. This method was proved simple, specific, sensitive, rapid and suitable for pharmacokinetics study of sitagliptin in human being.
Calibration ; Chromatography, Liquid ; Humans ; Liquid-Liquid Extraction ; Sitagliptin Phosphate ; blood ; pharmacokinetics ; urine ; Tandem Mass Spectrometry

Objective To study the 2-4 years intermediate-term clinical effects of bone-patellar tendon-bone (B-PT-B) autograft plus interface screw method and quadruple semitendinosus tendon autograft plus endobutton plate fixation method in anterior cruciate ligament (ACL) reconstruction after ACL injury and to estimate the correlation of various implants and fixation techniques with clinical effect. Methods A retrospective analysis was done on 104 cases with ACL injury as well as detailed clinical data from October 1998 to October 2000. ACL reconstruction with bone-patellar tendon-bone autograft (PT group) and kurosaka interface screw fixation were performed in 55 cases and quadruple semitendinosus tendon autograft and endobutton plate fixation (ST group) in 49 cases. The average follow up was 38.5 months in the PT group and 35.7 months in the ST group. We compared the intermediate myodynamic recovery, ROM, lachman test, pivot shift test, IKDC score, lysholm score, Werner score and X-ray view of tunnul enlargement between two groups. Results In the PT group, the circumference of thigh was (1.097?0.079) cm, shorter than that of normal side, and (0.896?0.126) cm in the ST group. The cases accounting for 82% (45/55) in the PT group and 88% (43/49) in the ST group had extension limitation less than 3?. Knee flexion limitation of 0?-5? accounted for 87% (48/55) in the PT group and 86% (42/49) in the ST group. Bilateral comparison of Lachman test less than 5 mm accounted for 93% (51/55) in the PT group and 96% (47/49) in the ST group. Negative rate of pivot shift test was 89% (47/55) in the PT group and 92% (45/49) in ST group. Bilateral comparison of AP knee laxity with 20Ib KT-1000 in laxity with less than 3 mm accounted for 53% (29/55) in the PT group and 57% (28/49) in the ST group. Lyoholm score in the PT group was increased from preoperative 69.2?6.4 to postoperative 86.7?4.3 and that in the ST group from 68.3?7.5 to 88.4?8.6. Knee motion standard of IKDC score in the PT group was 78%(43/55), which was found normal or nearly normal, and 82%(40/49) in the ST group. Patellar femoral pain Werner score was 43.0 ?6.1 in the PT group while 45.0?6.3 in the ST group. The X-ray showed that tunnel enlargement phenomena was 53% (29/55) in the PT group while 43% (21/49) in the ST group. Conclusions From 2-4 years intermediate-term follow up, there is no significant difference in ACL reconstruction using patellar tendon autograft plus interface screw method and quadruple semitendinosus tendon plus endobutton plate fixation method. Bone grafting in the donor site can reduce the incidence of anterior knee pain. Twisting technique is beneficial to overcome of the postoperative laxity caused by viscular elasticity of quadruple semitendinosus.

OBJECTIVE:To study the synthetic technique of magnesium gluconate METHODS:By taking gluconolactone and magnesium oxide as the semifinished materials,the synthetic technique of magnesium gluconate was optimized by orthogonal design RESULTS:The optimal preparing condition:gluconolactone∶magnesiumoxide(mol∶mol)was 1∶0 6;reaction temperature 100℃;reaction time 3 hours Under the optimal conditions,the drug were synthesized with a rate of total output over 95 0% CONCLUSION:This synthetic technique is stable in output rate,short in reaction period and feasible in operation

The work aims to study the drug metabolizing enzymes involved in the metabolism of butylphthalide and evaluate the induction and inhibition activities of butylphthalide on CYP450 isoenzymes by using in vitro (liver microsome incubation system of rats and human) and in vivo (CYP induced model of rats) method. Butylphthalide was incubated with selective inhibitors of CYP450, and its metabolic rate was determined to identify the metabolizing isoenzymes of NBP in rat (normal and induced rats) and human liver microsomes. The in vitro inhibition effect of butylphthalide on 6 main liver microsomal CYP450 isoenzymes was evaluated by using probe drugs; the induction and inhibition activities in vivo of butylphthalide on CYP450 isoenzymes were evaluated by NBP ig dosing (160 mg x kg(-1)) and iv dosing (20 mg x kg(-1)) in rats. After adding the specific inhibitors of CYP2C11, 2E1 and 3A 1/2 for rat, CYP2C19, 2E1 and 3A4/5 for human, the metabolism of NBP in rat and human liver microsomes were reduced 38.8%, 86.2%, 78.4% and 51.0%, 92.0%, 58.9% of control, respectively. The metabolic rates of NBP in CYP2E1 and 3A 1/2 induced rat liver microsomes were increased 25.5% and 68.9%. High concentration of NBP (≥ 200 μmol x L(-1), in vitro) could inhibit the activities of CYP1A2, 2C6, 2C11 and 2D2 in rats, and high concentration of NBP ( ≥ 15 μmol x L(-1), in vitro) could inhibit the activity of CYP2C19 in human. All the results indicated that NBP should be mainly metabolized by CYP2E1, 2C11 and 3A 1/2 in rats and CYP2E1, 2C19 and 3A4/5 in human. High concentration of NBP could inhibit human CYP2C19 in vitro. No significant induction/inhibition effects of NBP were observed on rat liver CYP450 isoforms after ig 160 mg x kg(-1) NBP or iv 20 mg x kg(-1) NBP.

A rapid and sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method for quantification of sitagliptin in human plasma and urine had been developed. This method was applied to the pharmacokinetics study of sitagliptin tablet after single- and multiple-dosing in Chinese population. Plasma samples were prepared by a liquid-liquid extracted method, and urine samples were diluted. Compounds were analyzed by multiple reaction monitoring (MRM) mode with a electrospray ionization (ESI) interface. Mobile phase consisted of methanol and water (85 : 15, v/v). The linear concentration range of calibration curve was 0.5-1 000 ng.mL-1. and 0.2-100 µg.mL , intra-run/between-run accuracy was 98.98%-103.69% and 97.63%-102.29%, intra-run/between-run precision was <5.51% and 4.26% for plasma and urine sample, respectively. The stability of sitagliptin stock solution was tested for 55 days at -30 °C. Sitagliptin was stable when stored under the following conditions: 24 hours in the autosampler after sample preparation; 24 hours at room temperature, after 3 freeze and thaw cycles (from -30 °C to room temperature), 40 days at -30 °C for plasma and urine samples. The absolute recovery in plasma was 71.1%, and no matrix effect was founded. This method was proved simple, specific, sensitive, rapid and suitable for pharmacokinetics study of sitagliptin in human being.

Objective To investigate the relationship of T peak-T end (Tp-Te) interval and Tp-Te interval disper-sion (Tp-Ted) in different periods of myocardial ischemia in patients with acute myocardial infarction (AMI), and to assess the clinical significance of Tp-Te and Tp-Ted for prediction of the ventricular arrhythmia (VA). Methods A total of 80 pa-tients with AMI were enrolled in the study. The sizes and changes of Tp-Te and Tp-Ted were observed during the acute phase and recovery phase in patients. The differences of Tp-Te and Tp-Ted were compared between ventricular tachycardia group (A group), ventricular premature beats group (B group) and non- ventricular arrhythmia group (C group). Results The values of Tp-Te and Tp-Ted were obviously longer in acute period [(125.22±17.70) ms and (54.76±13.26) ms] than those in recovery period[ (113.84±17.37) ms and (42.06±13.95)ms] (P<0.01). The values of Tp-Te and Tp-Ted were signifi-cantly longer in A group[ (134.82±19.56) ms and (62.00±15.19) ms] than those in B [(122.94±15.09) ms and (54.09±10.56) ms ]and C group [(110.09±15.21) ms and (45.27±9.85) ms]. The values were higher in B group than those of C group. Con-clusion The Tp-Te interval and Tp-Ted prolongated in acute phase than those of recovery phase in patients with AMI. Tp-Te interval and Tp-Ted can be used as an important index to predict VA in patients with AMI.

OBJECTIVE:To carry out the ISO9001standard quality control system in the department of pharmacy.METHODS:The procedures and methods of PDCA cycle(Plan-Do-Check-Action)were applied to our department's ISO9001quality authentication standardization.RESULTS:The application of PDCA cycle-based ISO9001standards proved to be successful in the standardization of our department.CONCLUTION:The ISO9001quality authentication following the PDCA cycle is effective.

Based on the character of the molecular structure, the prodrugs of phosphates and phosphonates were divided into two categories. The first is the drug which contained the phosphate group, introducing protected groups to increase lipophilicity and improve bioavailability. The other one is the drug which had no phosphate group, introducing the phosphate group into molecules to enhance the solubility, regulate the distribution coefficient and enhance the drug-like property. This review focuses on the application of phosphates and phosphonates in drug research and development based on improvement of physico-chemical property, drug safety and the pharmacokinetics.

Objective To understand the present situation and requirements of health education in schistosomiasis control in Hubei Province,so as to improve the health education to the targeted people. Method Through the questionnaire survey and field investigation,the data of the present situation and requirements of health education in schistosomiasis control were collect-ed in 24 counties(cities)of Hubei Province,and these data included the related institution structure of health education,basic information of personnel,equipment,funds,and health education working form. All the data collected were analyzed and evalu-ated. Results Among the 24 counties,there were 12 independent departments of health education,accounting for 50%. In terms of the basic information of the health education staff,the youngest person was 34 years old and the eldest was 58 years old,and the mean age was 46.55± 6.9 years. For the formal school education of the staff,5 had senior high school or below edu-cation (20.8%),16 had college education (66.7%),3 had bachelor degree or above (12.5%). There were 10 counties (41.70%)with the special funds for health education work but there were 3 counties(12.50%)without the special funds. Con-clusion The effectiveness of health education work in schistosomiasis control is remarkable,but there are still deficiencies in professional staff and funds in Hubei Province.

The work aims to study the drug metabolizing enzymes involved in the metabolism of butylphthalide and evaluate the induction and inhibition activities of butylphthalide on CYP450 isoenzymes by using in vitro (liver microsome incubation system of rats and human) and in vivo (CYP induced model of rats) method. Butylphthalide was incubated with selective inhibitors of CYP450, and its metabolic rate was determined to identify the metabolizing isoenzymes of NBP in rat (normal and induced rats) and human liver microsomes. The in vitro inhibition effect of butylphthalide on 6 main liver microsomal CYP450 isoenzymes was evaluated by using probe drugs; the induction and inhibition activities in vivo of butylphthalide on CYP450 isoenzymes were evaluated by NBP ig dosing (160 mg x kg(-1)) and iv dosing (20 mg x kg(-1)) in rats. After adding the specific inhibitors of CYP2C11, 2E1 and 3A 1/2 for rat, CYP2C19, 2E1 and 3A4/5 for human, the metabolism of NBP in rat and human liver microsomes were reduced 38.8%, 86.2%, 78.4% and 51.0%, 92.0%, 58.9% of control, respectively. The metabolic rates of NBP in CYP2E1 and 3A 1/2 induced rat liver microsomes were increased 25.5% and 68.9%. High concentration of NBP (≥ 200 μmol x L(-1), in vitro) could inhibit the activities of CYP1A2, 2C6, 2C11 and 2D2 in rats, and high concentration of NBP ( ≥ 15 μmol x L(-1), in vitro) could inhibit the activity of CYP2C19 in human. All the results indicated that NBP should be mainly metabolized by CYP2E1, 2C11 and 3A 1/2 in rats and CYP2E1, 2C19 and 3A4/5 in human. High concentration of NBP could inhibit human CYP2C19 in vitro. No significant induction/inhibition effects of NBP were observed on rat liver CYP450 isoforms after ig 160 mg x kg(-1) NBP or iv 20 mg x kg(-1) NBP.
Animals ; Benzofurans ; pharmacology ; Cytochrome P-450 Enzyme Inhibitors ; pharmacology ; Cytochrome P-450 Enzyme System ; metabolism ; Humans ; Isoenzymes ; metabolism ; Liver ; metabolism ; Microsomes, Liver ; metabolism ; Rats