Studies were performed in 20 patients with breast cancer, who received 26 cycles of high-dose cisplatin (100 mg/m2, IV. drip). In twenty-five cycles of them urinary Alb, IgG and NAG showed abnormal values. The patient...Studies were performed in 20 patients with breast cancer, who received 26 cycles of high-dose cisplatin (100 mg/m2, IV. drip). In twenty-five cycles of them urinary Alb, IgG and NAG showed abnormal values. The patients were divided into low-nephrotoxicity and high-nephrotoxicity groups by the degree of renal dysfunction. Thirty-five percent of the patients exhibited high-nephrotoxicity. These patients had significantly higher plasma and/ or urinary Pt peak levels during cisplatin (CP) infusion than did low-nephrotoxicity. 70 - 80% of the patients developed significant nephrotoxicity when urinary Pt peak level rose up to 40 fig/ml or plasma Pt peak level >4 μg/ml. It is quite important to reduce nephrotoxicity that urinary Pt level is controlled below 40 μg/ml and plasma Pt level <4 μg/ml. It is suggested that urine output should be maintained over 300 ml/hr during 2 hours before and after the end of infusion and >100 ml/hr during 3 days after the infusion. That may keep the nephrotoxicity of CP in less serious degree and easy to recover.展开更多
A sensitive and selective liquid chromatography-tandem mass spectrometric（LC —MS/MS）method was established to determine 2-oxo-clopidogrel,a crucial intermediate metabolite in human plasma.A chromatographic separati...A sensitive and selective liquid chromatography-tandem mass spectrometric（LC —MS/MS）method was established to determine 2-oxo-clopidogrel,a crucial intermediate metabolite in human plasma.A chromatographic separation was performed on a Sapphire C_（18） column following a liquid-liquid extraction sample preparation with methyl t-butyl ether.Detection was carried out on a triple quadrupole mass spectrometer operated in multiple reaction monitoring（MRM） with an electrospray ionization（ESI）mode.The method was validated in terms of specificity,accuracy,precision and limit of quantification.The calibration curves ranged from 0.50 to 50.0 ng/mL with good linearity.The stability was fully validated with addition of 1,4-dithio-DL-threitol（DTT） into the plasma sample prior to and in the preparation procedure.The validated method was proved to be suitable for use in pharmacokinetic study after single oral administration of 75 mg clopidogrel tablets in human subjects,which could make contribution to intensive study of the clinical drug-drug interactions of clopidogrel and individual treatment.展开更多
Simple,rapid and specific liquid chromatography-mass spectrometry（LC-MS） methods have been developed and validated for the quantification of cefcapene acid in human plasma and urine.Plasma samples were simply pretre...Simple,rapid and specific liquid chromatography-mass spectrometry（LC-MS） methods have been developed and validated for the quantification of cefcapene acid in human plasma and urine.Plasma samples were simply pretreated with methanol for deproteinization.Urine samples were briefly diluted with methanol-water（50：50,v/v）,and centrifuged to remove large particles.Chromatographic separation was performed on a Hedera ODS-2 column.For the plasma assay,the isocratic mobile phase consisted of 35% solvent A（Methanol） and 65% solvent B（10 mM ammonium acetate buffer solution containing 0.2% folic acid） with a flow rate of 0.3 mL/min.For the urine assay,the isocratic mobile phase consisted of 30% solvent A（Methanol） and 70% solvent B（10 mM ammonium acetate buffer solution containing 0.2% folic acid） with a flow rate of 0.3 mL/min.The assays were linear over the concentration ranges of 0.03-5 μg/mL in plasma and 0.1-400 μg/mL in urine,and were successfully applied to a pharmacokinetic study after single and multiple oral administrations of cefcapene pivoxil hydrochloride tablets in healthy Chinese volunteers.展开更多
The present study was designed to develop and validate a rapid, sensitive, and reliable ultra-high performance liquid chromatography coupled with tandem mass spectrometry(UHPLC-MS/MS) method for the simultaneous deter...The present study was designed to develop and validate a rapid, sensitive, and reliable ultra-high performance liquid chromatography coupled with tandem mass spectrometry(UHPLC-MS/MS) method for the simultaneous determination of five major active constituents in the traditional Chinese medicinal preparation Xingxiong injection(XXI) in rat plasma, including quercetin 3-O-rutinoside(QCR), kaempferol 3-O-rutinoside(KFR), isorhamnetin 3-O-rutinoside(ISR), bilobalide(BB), and ligustrazine(LGT). The plasma samples were pretreated by protein precipitation with acetonitrile. The chromatographic separation was achieved on a Waters Symmetry C18 analytical column(2.1 mm × 100 mm, 3.5 mm) with a mobile phase of 0.1% aqueous formic acid(A)-acetonitrile(B). Quantitation of the five bioactive constituents was achieved. Naringin was used as the internal standard(IS). All the calibration curves showed good linearity(r > 0.996) over the concentration range, with the lowest limit of quantification(LLOQ) between 2-18 ng·m L^(-1). The intraand inter-day accuracy and precision of the analytes were both within acceptable limits. Moreover, satisfactory extraction recoveries(90.92%-104.03%) were obtained by protein precipitation. The validated method was successfully applied to a pharmacokinetic study of XXI in rats after intravenous administration at three doses. The pharmacokinetic parameters of the five compounds varied in a dose-dependent manner within the tested dosage range. The present study was the first report of pharmacokinetic study for XXI.展开更多
文摘Studies were performed in 20 patients with breast cancer, who received 26 cycles of high-dose cisplatin (100 mg/m2, IV. drip). In twenty-five cycles of them urinary Alb, IgG and NAG showed abnormal values. The patients were divided into low-nephrotoxicity and high-nephrotoxicity groups by the degree of renal dysfunction. Thirty-five percent of the patients exhibited high-nephrotoxicity. These patients had significantly higher plasma and/ or urinary Pt peak levels during cisplatin (CP) infusion than did low-nephrotoxicity. 70 - 80% of the patients developed significant nephrotoxicity when urinary Pt peak level rose up to 40 fig/ml or plasma Pt peak level >4 μg/ml. It is quite important to reduce nephrotoxicity that urinary Pt level is controlled below 40 μg/ml and plasma Pt level <4 μg/ml. It is suggested that urine output should be maintained over 300 ml/hr during 2 hours before and after the end of infusion and >100 ml/hr during 3 days after the infusion. That may keep the nephrotoxicity of CP in less serious degree and easy to recover.
文摘A sensitive and selective liquid chromatography-tandem mass spectrometric（LC —MS/MS）method was established to determine 2-oxo-clopidogrel,a crucial intermediate metabolite in human plasma.A chromatographic separation was performed on a Sapphire C_（18） column following a liquid-liquid extraction sample preparation with methyl t-butyl ether.Detection was carried out on a triple quadrupole mass spectrometer operated in multiple reaction monitoring（MRM） with an electrospray ionization（ESI）mode.The method was validated in terms of specificity,accuracy,precision and limit of quantification.The calibration curves ranged from 0.50 to 50.0 ng/mL with good linearity.The stability was fully validated with addition of 1,4-dithio-DL-threitol（DTT） into the plasma sample prior to and in the preparation procedure.The validated method was proved to be suitable for use in pharmacokinetic study after single oral administration of 75 mg clopidogrel tablets in human subjects,which could make contribution to intensive study of the clinical drug-drug interactions of clopidogrel and individual treatment.
文摘Simple,rapid and specific liquid chromatography-mass spectrometry（LC-MS） methods have been developed and validated for the quantification of cefcapene acid in human plasma and urine.Plasma samples were simply pretreated with methanol for deproteinization.Urine samples were briefly diluted with methanol-water（50：50,v/v）,and centrifuged to remove large particles.Chromatographic separation was performed on a Hedera ODS-2 column.For the plasma assay,the isocratic mobile phase consisted of 35% solvent A（Methanol） and 65% solvent B（10 mM ammonium acetate buffer solution containing 0.2% folic acid） with a flow rate of 0.3 mL/min.For the urine assay,the isocratic mobile phase consisted of 30% solvent A（Methanol） and 70% solvent B（10 mM ammonium acetate buffer solution containing 0.2% folic acid） with a flow rate of 0.3 mL/min.The assays were linear over the concentration ranges of 0.03-5 μg/mL in plasma and 0.1-400 μg/mL in urine,and were successfully applied to a pharmacokinetic study after single and multiple oral administrations of cefcapene pivoxil hydrochloride tablets in healthy Chinese volunteers.
基金financially supported from National Natural Science Foundation of China(Nos.81673569,and 81473343)Program for New Century Excellent Talents in University(No.NECT-13-1034)a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions
文摘The present study was designed to develop and validate a rapid, sensitive, and reliable ultra-high performance liquid chromatography coupled with tandem mass spectrometry(UHPLC-MS/MS) method for the simultaneous determination of five major active constituents in the traditional Chinese medicinal preparation Xingxiong injection(XXI) in rat plasma, including quercetin 3-O-rutinoside(QCR), kaempferol 3-O-rutinoside(KFR), isorhamnetin 3-O-rutinoside(ISR), bilobalide(BB), and ligustrazine(LGT). The plasma samples were pretreated by protein precipitation with acetonitrile. The chromatographic separation was achieved on a Waters Symmetry C18 analytical column(2.1 mm × 100 mm, 3.5 mm) with a mobile phase of 0.1% aqueous formic acid(A)-acetonitrile(B). Quantitation of the five bioactive constituents was achieved. Naringin was used as the internal standard(IS). All the calibration curves showed good linearity(r > 0.996) over the concentration range, with the lowest limit of quantification(LLOQ) between 2-18 ng·m L^(-1). The intraand inter-day accuracy and precision of the analytes were both within acceptable limits. Moreover, satisfactory extraction recoveries(90.92%-104.03%) were obtained by protein precipitation. The validated method was successfully applied to a pharmacokinetic study of XXI in rats after intravenous administration at three doses. The pharmacokinetic parameters of the five compounds varied in a dose-dependent manner within the tested dosage range. The present study was the first report of pharmacokinetic study for XXI.
