Objective To investigate the association between genetic polymorphisms of cytochrome P450 MSP1 gene and the glutathione s-transferase GSTM1 gene in female workers exposed to aromatic solvents and spontaneous abortion. Methods A retrospective epidemiological investigation was carried out among 276 female workers including 58 female workers with history of spontaneous abortion and 218 female workers without spontaneous abortion selected in Yanshan of Beijing by the trained investigators using the unified questionnaire. Results The spontaneous abortion of female workers was significantly associated with GSTM1 (absent) (OR=2.07, 95% CI: 1.15-3.71), but not MSP1 (present) and exposure to aromatic solvent. After adust-ment for major confounders including education, age, shift work, body mass index, passive smoking and occupational stress, the multiple logistic regression analysis showed that GSTM1 gene (absent) significantly increased the risk of spontaneous abortion of female workers (OR=2.15, 95% CI: 1.17-3.98). Before and after adjustment for major confounders including education, age, shift work, body mass index, passive smoking and occupational stess, the multiple regression analysis showed that GSTM1 (absent) combined with MSP1 (heterozygous variant type / homozygous variant type) significantly increased the risk of spontaneous abortion (OR=2.98, 95% CI:l. 17-7.59), using the group with GSTM1 (present) and MSP1 (homozygous wild type) as reference group. Conclusion Our data suggested a genetic influence on spontaneous abortion in this population, GSTM1 (absent) was significantly associaled with spontaneous abortion, also provide evidence of additional joint action of gene MSP1 (heterozygous variant type and homozygous variant type) and GSTM1 (absent) to spontaneous abortion.

During the period of peri-operation on gallbladder,T2MD patients with calculous cholecystitis were randomly divided into groups of continuous subcutaneous insulin infusion(CSII,n=32),multiple subcutaneous insulin injection(MSII,n=48) and OHA(n=64).It is found that CSII has better glucose control than MSII and OHA.

Chlorogenic acid (5-CQA) is one of the major components in some Chinese herbal injections. However, the metabolism of 5-CQA in rats after intravenous injection has not been determined. An ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) method was applied to identify the metabolites in bile, urine, feces and plasma after a single intravenous administration of 10 mg x kg(-1) 5-CQA to rats. Using MSE and mass defect filter techniques, a total of 35 metabolites were detected in bile, urine, feces and plasma. The predominant metabolites in bile were glutathione conjugates of O-methyl-5-CQA, accounting for approximately 80% of the metabolites excreted in bile. The major components in urine were parent drug, O-methyl-5-CQA, hydrolyzed metabolites and glucuronide conjugates. The major components in feces were O-methyl-5-CQA and its cysteine conjugates. The major component in plasma was the parent drug. The urinary and fecal excretion pathways were equally important to 5-CQA in rats. These results demonstrate that 5-CQA undergoes extensively metabolism in rats and are highly reactive to nucleophiles such as GSH. This finding indicates that attention should be paid on the injections containing 5-CQA, which may covalently bind to proteins, leading to allergenic drug reactions.

A chiral LC-MS/MS method for the simultaneous analysis of desvenlafaxine (DVS) enantiomers in human plasma was developed and applied to a pharmacokinetic study on 12 Chinese healthy volunteers. d6-Desvenlafaxine was used as internal standard (IS). Chromatographic separation was performed on the Astec Chirobiotic V chiral column (150 mm x 4.6 mm, 5 μm). The assay was linear over the concentration range of 0.500-150 ng x mL(-1) for both enantiomers (r2 > 0.99). The method was successfully applied to a stereoselective pharmacokinetic study of 100 mg desvenlafaxine sustained release tablets on 12 Chinese healthy volunteers under fasting conditions. The results showed that the pharmacokinetic parameters were similar to both enantiomers in Chinese healthy volunteers. The AUC(0-t), and C(max) of the two enantiomers were about 1.5 times higher than those of blacks and whites reported in the literature.

The study aims to evaluate the bioequivalence of valsartan hydrochlorothiazide tablets, and to investigate the potential cause of bioinequivalence. This was a single-center study with an open, randomized double-way crossover design. Test and reference preparations containing 160 mg of valsartan and 25 mg of hydrochlorothiazide were given to 36 healthy male volunteers. Plasma concentrations of valsartan and hydrochlorothiazide were determined simultaneously by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated, while the bioequivalence between test and reference preparations were evaluated. The dissolution profiles of test and reference preparations in four different mediums were determined via dissolution test and HPLC. The similarity was investigated according to the similarity factors (f2). The F(o-t) and F(0-infinity) were (139.4 +/- 65.2)% and (137.5 +/- 61.2)% for valsartan of test preparations. It led to get the conclusion that test and reference preparations were not bioequivalent for valsartan. A significant difference was observed between test and reference tablets in the valsartan dissolution test of pH 1.2 hydrochloric acid solution. The key factor of the bioinequivalence might be that dissolution of valsartan in acid medium has marked difference between two preparations.

To study the metabolite excretion of theophylline, a rapid and specific method by liquid chromatography with heated electrospray ionization tandem mass spectrometry (LC-HESI/MS/MS) method for simultaneous determination of theophylline, 1, 3-dimethyluric acid (1,3-DMU), 3-methylxanthine (3-MX) and 1-methyluric acid (1-MU) in human urine was developed using theophylline-d6 and 5-fluorouracil as internal standards. Selected reaction monitoring (SRM) with heated electrospray ionization (HESI) was used in the negative mode for mass spectrometric detection. After diluted with methanol and centrifuged, the analytes and ISs were separated on a XDB-Phenyl (150 mm x 4.6 mm, 5 microm) column with a mixture of water-methanol-formic acid (30 : 70 : 0.15) as mobile phase at a flow rate of 0.6 mL x min(-1). The linear calibration curves for theophylline, 1, 3-DMU, 3-MX and 1-MU were obtained in the concentration range of 1.0-250 microg x mL(-1), separately. The method herein described is effective and convenient, and can be used for determination of theophylline and its three metabolites. The results showed that urinary excretion ratio of theophylline, 1,3-DMU, 3-MX and 1-MU is approximately 1 : 3 : 1 : 2 in Chinese subjects, which is similar to the reported excretion pattern in Caucasian.

The study aims to develop a rapid, sensitive and specified method of liquid chromatography with heated electrospray ionization tandem mass spectrometry (LC-HESI/MS/MS) for simultaneous determination of amlodipine, benazepril and benazeprilat in human plasma using amlodipine-d4 and ubenimex as internal standards (ISs). Selected reaction monitoring (SRM) with heated electrospray ionization (HESI) was used in the positive mode for mass spectrometric detection. Analytes and ISs were extracted from plasma by simple protein precipitation. The reconstituted samples were chromatographed on a C18 (100 mm x 4.6 mm, 5 microm) column with mixture of methanol-acetonitrile-5 mmol.L- ammonium acetate-formic acid (30 : 30 : 40 : 0.1) as mobile phase at a flow rate of 0.6 mL.min-1. The standard curves were demonstrated to be linear in the range of 0.02 to 6.00 ng.mL-1 for amlodipine, 0.2 to 1,500 ng.mL-1 for benazepril and benazeprilat with r2>0.99 for each analyte. The lower limit of quantitation was identifiable and reproducible at 0.02, 0.2 and 0.2 ng mL-1 for amlodipine, benazepril and benazeprilat, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limit across all concentrations. The plasma samples were stable after four freeze-thaw cycles and being stored for 93 days at -20 degrees C. The method was applied to a pharmacokinetic study of a fixed-dose combination of amlodipine and benazepril on Chinese healthy volunteers.

To study the drug-drug interaction of morinidazole and warfarin and its application, a sensitive and rapid liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of R-warfarin/S-warfarin in human plasma. In a random, two-period crossover study, 12 healthy volunteers received a single oral dose of 5 mg racemic warfarin in the absence and presence of morinidazole. Blood samples were collected according to a pre-designed time schedule. R-warfarin, S-warfarin and methyclothiazide were extracted with ethylether : methylenechloride (3 : 2), then separated on a Astec Chirobiotic V (150 mm x 4.6 mm ID, 5 microm) column using 5 mmol x L(-1) ammonium acetate (pH 4.0) - acetonitrile as mobile phase at a flow-rate of 1.5 mL x min(-1). The mobile phase was splitted and 0.5 mL x min(-1) was introduced into MS. A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the negative ion mode. Quantification was performed using multiple reaction monitoring (MRM). The resolution of warfarin enantiomers is 1.56. The linear calibration curves for R-warfarin and S-warfarin both were obtained in the concentration range of 5 - 1 000 ng x mL(-1). Intra- and inter-day relative standard deviation (RSD) for R-warfarin and S-warfarin over the entire concentration range across three validation runs was both less than 10%, and relative error (RE) ranged from -4.9% to 0.7%, separately. The method herein described is effective and convenient, and suitable for the study of metabolic interaction between morinidazole and warfarin. The results showed that coadministration of warfarin with morinidazole did not affect the pharmacokinetics of either R-warfarin or S-warfarin.

Objective:To evaluate the diagnostic accuracy of 64-channel multislice spiral computed tomography(MSCT) in subjects with presentations suggestive of stable angina or acute coronary syndrome. Methods: Subjects received both 64-channel MSCT and coronary angiography, from Feb. 2006 to Feb. 2007, were enrolled for retrospective analyses. Results of the quantitative coronary angiography were used as the "Golden criteria", accuracy of 64-channel MSCT were evaluated in the overall sample, as well as in subjects suspected of stable angina and acute coronary syndrome. Results: A total of 120 subjects were enrolled in the analyses. On the patient level, the sensitivity, specificity, and accuracy of 64-channel MSCT in detecting significant stenoses were 92.5%, 50%, and 87.5%, respectively. The overall ROC area under curve was 0.71. On the artery level, sensitivity, specificity, positive predictive value, negative predictive value, and ROC area under curve of 64-channel MSCT were 69.9%, 83.8%, 81.1%, 73.7%, and 0.77, respectively. Further analyses showed the sensitivity, specificity, positive predictive value, negative predictive value, and ROC area under curve of 64-channel MSCT in subjects presenting as stable angina and in subjects presenting as acute coronary syndrome were as follows: 70.2% vs 69.2%, 76.2% vs 86.0%, 74.7% vs 85.6%, 71.9% vs 69.9%, and 0.73 vs 0.78. Conclusion: The accuracy rates of 64-chanel MSCT in subjects presenting as stable angina and in subjects presenting as acute coronary syndrome were similar.

AIM　To develop a sensitive and specific LC/MS/MS method for determination of amlodipine in human plasma. METHODS　Amlodipine and internal standard 4′-hydroxypropafenone were extracted from plasma using liquid-liquid extraction, then separated on a Zorbax C8 column. The mobile phase consisted of acetonitrile-water-formic acid (75∶35∶1), at a flow-rate of 0.4 mL*min-1. A Finnigan TSQ tandem mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode. Selected reaction monitoring (SRM) using the precursor → product ion combinations of m/z 409 → 238 and m/z 358 → 116 was used to quantify amlodipine and internal standard, respectively. RESULTS　The linear calibration curves were obtained in the concentration range of 0.4-16.0 ng*mL-1. The limit of quantification was 0.4 ng*mL-1. Each plasma sample was chromatographed within 3.7 min. The method was successfully used in several pharmacokinetic studies for amlodipine. More than 1 500 plasma samples were assayed within two weeks. CONCLUSION　The method is proved to be suitable for clinical investigation of amlodipine pharmacokinetics, which offers advantages of specificity, speed, and greater sensitivity over the previously reported methods.