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Objective: To develop an LC-MS/MS method for the determination of donepezil and rivastigmine in human serum. Methods: After protein precipitation with 600μl acetonitrile, the serum samples were analyzed by LC-MS/MS. Using loratadine as the internal standard, a Waters Xselect CSH C18(150 mm×3 mm, 2. 5 μm) column was used with the mobile phase consisting of water (containing 10 mmol·L-1ammonium acetate)-acetonitrile(20 ∶ 80)at a flow rate of 0. 4 ml·min-1with the column temperature at 40 ℃. The ion transitions were performed in a positive electrospray ionization multiple reaction-monitoring mode regarding [M+H] +as the molecular ion peak of donepezil and rivastigmine monitored with m/z 380. 1→m/z 91. 1 and m/z 251→m/z 206. 5, respectively. The internal standard was monitored with m/z 383. 1→m/z 337. 1. Results: The linear range of donepezil and rivastigmine was 0. 5-400 ng·ml-1(r>0. 99) and the lowest quantification limit was 0. 5 ng·ml-1. For donepezil, the intra-day and inter-day RSD was 2. 06% to 12. 51% , the relative error was -6. 60% to 4. 20% , and the relative recovery was ranged from 80. 76% to 96. 17% (RSD<15% ). For rivastigmine, the intra-day and inter-day RSD was 1. 69% to 9. 31% , the relative error was -5. 58% to 5. 20% , and the mean relative recovery was ranged from 96. 69% to 100. 15% (RSD<15% ). For the two compounds, the serum samples were stable at -40℃ for 75 d and kept stable after three repeated freeze-thaw cycles. The prepared samples were stable in the automatic sample injector (4℃) for 5 h (RSD<15% ). Conclusion: The developed assay method can be applied in the therapeutic monitoring and pharmacokinetic study of donepezil and rivastigmine in human serum.
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Objective To summarize the clinical experience of patient diagnosed with Niemaoh-Pick disease being pregnant after liver transplantation. Methods Clinical data of one case of type B Niemaoh-Pick disease being pregnant after liver transplantation were retrospectively analyzed. Results The patient successfully underwent liver transplantation combined with splenic artery ligation on July 8, 2011. She was well recovered postoperatively. After surgery, she received conventional anti-rejection treatment, and gradually switched to use of tacrolimus at a dosage of 2.5 mg/d. The serum drug concentration was maintained at 2 ng/mL. In September 2015, she was successfully pregnant. On June 2, 2016, she delivered a male infant through cesarean section. She could breastfeed the infant in a low quantity early after delivery. Both the mother and infant were followed up until submission date. The mother was physically stable and the infant grew normally. Conclusions Patients diagnosed with Niemaoh-Pick disease can obtain favorable clinical outcomes of pregnancy and delivery after liver transplantation.
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Objective To understand the changing characteristics of drug concentration in the serum and cerebrospinal fluid(CSF) after intravenous (IV) drip of norvancomycin in patients after neurosurgery procedure.Methods Patients with surgical cavity/ventricular drainages after neurosurgery procedure in a hospital in 2014 were selected, and they were divided into 2 groups according to the administration modes (12 in each group), conventional administration group: 0.8 g norvancomycin IV drip for 60 minutes, repeated every 12 hours;continuous administration group, 0.8 g norvancomycin, IV drip for 60 minutes, followed by 0.4 g of IV drip for 11 hours, then 0.4 g for 12 hours, serum and CSF specimens were collected at different time points after administration, concentration of norvancomycin was determined.Results Serum norvancomycin concentration reached a peak of (55.52±26.04) and (59.22±41.88) mg/L in conventional administration group and continuous administration group respectively, 24-hour serum concentration were (8.21±6.04) and (9.11±5.09)mg/L respectively;CSF norvancomycin concentration reached a peak of (16.31±11.15) and (8.82±8.91)mg/L in conventional administration group and continuous administration group respectively, 24-hour CSF concentration were (6.12±2.34)and (5.71±4.72)mg/L respectively;CSF penetration rate of conventional administration group was calculated by ratio of area under curve (AUCCSF/AUCserum), at 0-12 and 12-24 h hour were 63.3% and 59.0% respectively;in continuous administration group were 25.4% and 47.4% respectively.According to 95% of the minimum inhibitory concentration (MIC90) 2 mg/L of target bacteria methicillin-resistant Staphylococcus aureus (MRSA), AUC0-24/MIC90 in conventional administration group and continuous administration group were 192 and 184 respectively.Conclusion For patients who receives early use of standard dose of norvancomycin after neurosurgery procedure, CSF drug concentration after convention and continuous administration of norvancomycin can both reach MIC90 against target bacteria.
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Objective To investigate the relationship between serum 10-hydroxycarbazepine (MHD, the main active metabolite of oxcarbazepine) concentration and oxcarbazepine efficacy and safety, and to optimize rational use of oxcarbazepine. Methods A total of 553 patients were enrolled in a self-controlled and open-label trial to assess the efficacy and safety of oxcarbazepine as monotherapy. The steady state serum MHD trough concentrations after dose were determined by SPE-HPLC. The relationship between MHD level and efficacy were evaluated by logistic regression model and receiver operating characteristic (ROC) curve. Results A total of 498 patients (90.1%) were effective and 404 patients (73.1%) were seizure free after oxcarbazepine monotherapy in this study. The clinical therapeutic range of steady state serum MHD trough concentrations observed in this study was 5 - 20 mg ? L-1 , and the corresponding 95% distribution interval of oxcarbazepine daily dose was 9. 0 -34.5 mg?kg-1?d-1 . Logistic regression results indicated a positive correlation of antiepileptic efficacy with serum MHD trough concentration within 0.9-30.0 mg?L-1 . The ROC area (95% confidence interval) of MHD trough concentration as the predictor for efficacy was 0.964 (0.938- 0.990), which showed accurate predictions. Most of patients whould have good antiepileptic efficacy while the steady-state serum MHD trough concentration remains above 8 mg?L-1 . Adverse effects were observed in 104 patients (18.8%) during oxcarbazepine dose escalation phase, and 23 patients (4.2%) during maintenance phase. There were no severe adverse effects associated with oxcarbazepine in this study. Patients with serum MHD concentrations >20 mg?L-1 were at greater risk of developing adverse effects. Conclusion Oxcarbazepine therapeutic efficacy and safety are associated with MHD trough level closely, so it is necessary to monitor MHD concentration.
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Objective To analyze the relationship between plasma concentration and efficacy , adverse drug reactions by monitoring vancomycin serum concentrations for appropriately treating the infections caused by methicillin‐resistant Staphylococcus aureus or other gram‐positive cocci .Methods Vancomycin concentration was monitored in the patients with indications for vancomycin therapy .Blood sample was taken after vancomycin was administered for at least 4 doses .The blood sample collected within 30 minutes before dosing was used to determine the trough blood concentration .The samples were taken within 30 minutes to 1 hour after infusion of vancomycin were used to estimate the peak concentration by fluorescence polarization immunoassay .The clinical data were collected at the same time to analyze clinical efficacy and safety .Results Vancomycin trough concentration ranged from 3 .22 mg/L to 50 .79 mg/L in 25 patients ,specifically ,＜ 5 mg/L in 3 cases ,5‐＜10 mg/L in 11 cases ,10‐15 mg/L in 3 cases ,and > 15 mg/L in 8 csaes .Peak concentration ranged from 13 .57 mg/L to 60 .47 mg/L ,specifically ,＜ 25 mg/L in 14 cases ,25‐40 mg/L in 7 cases ,and > 40 mg/L in 4 cases .The infection was cured in 80 .0% (20/25) of the patients .The gram‐positive cocci were eradicated in 87 .5% (21/24) of the patients .The dosage of vancomycin was adjusted in 13 patients according to the results of blood concentration monitoring .Majority of these patients (12/13 ,92 .3% ) were cured .Renal impairment was observed in 4 patients .Conclusions Vancomycin is safe and effective in treatment of methicillin‐resistant Staphylococcus aureus and other gram‐positive bacterial infections . Vacomycin concentration varies from person to person . Serum concentration monitoring is required to achieve best outcomes and the goal of individualized treatment of vancomycin.
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OBJECTIVE:To establish an ion-pair RP-HPLC method for determination of the concentration of netilmicin sulfate in human serum.METHODS:The determination was performed on Luna C18 column with column temperature set at 40℃;the mobile phase consisted of acetonitrile-water (15∶85,pH 2.0,containing 10 mmol?L-1 sodium heptanesulfonate) at a flow rate of 0.8 mL?min-1.The detection wavelength was set at 205 nm.RESULTS:The linear range of netilmicin was 2～20 mg?L-1(r=0.997 6) with a recovery rate of 93.66%～96.05%.The intra-day and inter-day RSD were both less than 10%,respectively.CONCLUSION:The method is sensitive and simple with accurate and reliable results,and it is able to satisfy the requirement for the determination of serum concentration of netilmicin.
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OBJECTIVE:To establish an RP-HPLC analysis of Carthamin in mice and to study its pharmacokinetics.METHODS:The serum concentration of Carthamin was determined by RP-HPLC.The blood concentration-time curve was established and the main pharmacokinetic parameters were computed.RESULTS:The linear range of Carthamin was 0.558～55.8 ?g?L-1(r=0.999 2),with the lowest limit of detection at 0.005 ?g?L-1Carthamin in vivo assumed two-compartment model and rapid absorption.CONCLUSION:The proposed method is simple,sensitive and reproducible,and it met the standard for pharmacokinetic study.
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0.05),but the t1/2 was longer and the AUC and the Cmax were lower in group B than in other groups(P
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OBJECTIVE: To determine the concentration of phenobarbital(PBB) in serum by RP-HPLC.METHODS: The analytical column was C18.The mobile phase consisted of methanol-water(44∶56) at a flow rate of 1.0 mL?min-1.The detection wavelength was set at 205 nm and the temperature of column was set at 35℃.RESULTS: A good linear relationship was obtained for PBB at a concentration range from 5.08 ?g?mL-1 to 63.50 ?g?mL-1(r=0.999 9).The mean relative recovery was 99.75% and the mean extraction recovery was 96.34%.The intra-day RSD and the inter-day RSD were all less than 4%.CONCLUSION: This method is simple,rapid,accurate,and suitable for therapeutic drug monitoring.
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OBJECTIVE: To establish a simple and rapid HPLC method for the determination of serum concentration of isofosfamide.METHODS: With cyclophosphamide as internal standard,the serum sample was extracted on C18 solid phase extraction column and determined on Zorbox-ODS C18 at room temperature.The mobile phase consisted of acetonitrile-water(25∶75) at a flow rate of 1 mL?min-1 and a detection wavelength of 200 nm.RESULTS: The linear range of ifosfamide was 2.5～200 ?g?mL-1(r=0.999 9),with the lowest detectable limit at 0.5 ?g?mL-1(S/N=3).Both the intraday and interday RSD were less than 5%.The extraction recoveries of ifosfamide at high,middle and low concentrations were ranged between 89.3% and 93.6% versus 77.6%～82.3% in chloroform-treated serum samples.CONCLUSION: The method which uses the C18 solid phase extraction column is of high recovery,and the sample treatment by which is simple,rapid,accurate,and pollution-free,and it is applicable for the monitoring of serum concentration and pharmacokinetic study of isofosfamide.
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OBJECTIVE:To determine the serum concentration of Deoxyschisandrin by RP-HPLC.METHODS:The chr-omatographic separation was performed on Phenomenex C18(250mm?4.6mm,5?m) column with column temperature at 30℃.The mobile phase consisted of methanol - water (80∶20) at a flow rate of 1mL?min-1. The detection wavelength was set at 252nm. RESULTS:The calibration curve of Deoxyschisandrin was linear in the concentration range from 0.52 to 33.28?g?mL-1 (r=0.999 6). The average recovery of deoxyschisandrin was (97.27?4.11)%(RSD=4.23%,n=9).CONCLUSION:The method is simple, accurate and sensitive, and it can be used for the determination of serum concentration of Deoxyschisandrin.
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OBJECTIVE:To establish a RP-HPLC method for the determination of the concentration of moxifloxacin in human serum.METHODS:The separation of sample was performed on Gemini C18 column with a fixed sample injection volume of 20?L.The mobile phase was methanol-water-triethylamine(112.5∶208.9∶0.06) at a flow rate of 1mL?min-1.The UV detective wavelength was set at 289nm;the column temperature was 25℃ and the sensitivity was 0.01AUFS.RESULTS:In the range of 0.312 5～10?g?mL-1(r=0.999 8),moxifloxacin showed a good linear relation in HPLC.The recoveries of moxifloxacin at three concentrations(10,2.5,0.625?g?mL-1) were 99.46%,103.12%,and 96.14%,respectively,with intra-day RSD at 3.27%,3.35%,0.92%,respectively and inter-day RSD at 7.19%,6.25%,6.68%,respectively.CONCLUSION:This method is simple,rapid,accurate and sensitive,and it can be used for the concentration determination and the pharmacokinetic study of moxifloxacin.
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OBJECTIVE:To establish a HPLC method for determination of the concentration of Buspirone in serum.MET_ HODS:The chromatographic system consisted of ZORBA SB-C 18 column and mobile phase of methanol-acetonitrile-water-0.1mol/L NaAC buffer solution(pH4.5)(10∶38∶51∶1),with a detection wavelength of237nm,and the content was calcu?lated by peak area internal standard method.RESULTS:The linear range of Buspirone was1～80ng/ml,r=0.9979.CONCL_ USION:This method is simple and accurate for determination of Buspirone in serum.
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OBJECTIVE:To evaluate the efficacy and toxicity of paclitaxel combined with cisplatin in the treatment of advanced non-small cell lung cancer(NSCLC) by weekly-,biweekly- and three-weekly-regimens.METHODS:180 patients who had been confirmed by pathology and cytology as having NSCLC(Ⅲ～Ⅳstage) were enrolled into the study and divided to three groups:Biweekly - regimen(n= 60):paclitaxel 80 mg?m~(-2) plus cisplatin 40 mg?m~2 ivgtt on day 1 and day 8 in every 21 days;Weekly- regimen(n= 60):paclitaxel 55 mg?m~(-2) plus cisplatin 30 mg?m z ivgtt on day 1,8,and 15 in every 28 days;Three - weekly regimen(n = 60):paclitaxel 160 mg?m~(-2) plus cisplatin 80 mg?m~(-2) ivgtt on day 1 in every 21 days.Serum concentrations of paclitaxel at 3,12,24 h after administration were determined,and the efficacy and toxicity after two- cycle treatment were evaluated.RESULTS:The overall response rates of weekly-,biweekly -and three weekly regimens were 43.1%,35.8%and 34.0%respectively,showing no statistical differences among groups,but the incidence of main toxicities of biweekly-regimen was lower as compared with the other regimens.CONCLUSION:Biweekly -regimen is optimal for the treatment of advanced NSCLC with mild toxicity,which deserves to be applied in clinical practice.
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OBJECTIVE:To observe the factors that influence the fluctuation of serum concentrations of valproic acid and to improve the effectiveness and usefulness of monitoring the serum concentration.METHODS:The factors that influence the serum concentration of valproic acid were summed up and the countermeasures were put forward.RESULTS:These influencing factors included the drug administration time;the blood sampling time;the right moment for monitoring;the dosage forms and quality of drug;the obedience of patient;combining use of drugs and the physiological and pathological conditions of pa?tients.CONCLUSION:When epileptic patients receive long-term medical treatment,the doctor,the patient and the pharma?cist should communicate mutually,establish the relevant data,pay attention to those factors and ensure the patients safe and effective in use of drug.
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OBJECTIVE:To determine the content of epirubicin in human plasma by RP-HPLC.METHODS:The chromatographic separation was performed on YWG C18 column.The mobile phase consisted of water-acetonitrile(12∶7,with pH adjusted to 3.90?0.05 using 85% phosophoric acid)at a flow rate of 1.0 mL?min-1.The detective wavelength was set at 254 nm.RESULTS:The linear range of epirubicin was 0.12～4.80 mg?L-1(r=0.998 4)with the lowest detective range of 0.01 mg?L-1.The intraday RSD was less than 4.40% and the inter-day RSD was less than 5.60%,and the average recovery rate was 99.40%(RSD=4.02%).The sample solution was stable within 12 h under room temperature.CONCLUSION:The method is easy,precise and reproducible to operate and the result of the determination is accurate.