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Objective: To establish a method for the rapid determination of acetaminophen (APAP) in human plasma by LC-MS/MS. Methods: The plasma samples were extracted by methanol and acetonitrile (1: 1) and purified directly. C(18) column was used for sample separation. The mobile phase were methanol (5 mmol/L ammonium acetate) and water (5 mmol/L ammonium acetate). Samples were analyzed by LC MS/MS with the electrospray ionization multi reaction monitoring (MRM) mode. Results: The calibration curves of APAP was linear in the concentration range of 0~10 mg/L, the correlation coefficient (r) was greater than 0.999 0. The relative standard deviation within and between batches was less than 10%. The recovery rate were 96.81%~101.7%. The detection limit of the method was 0.1 μg/L and the lower limit of quantification was 0.3 μg/L. Conclusion: This method has strong specificity, high sensitivity and reliable determination results. It is suitable for the rapid analysis of clinical plasma samples.
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Humans , Chromatography, Liquid/methods , Acetaminophen , Tandem Mass Spectrometry/methods , Methanol , Chromatography, High Pressure Liquid/methodsABSTRACT
Objective To explore the role of clinical pharmacists in the treatment of drug poisoning by analyzing the clinical pharmacist's participation in the treatment of a patient with sodium valproate poisoning. Methods Clinical pharmacists measured the plasma concentration of sodium valproate to inform the doctor to diagnose illnesses. At the initial stage when the concentration is high, to eliminate the free drug by continuous venous-venous hemodialysis-filtration (CVVHDF). Then, the combined drug was cleared by hemoperfusion (HP). Results The blood concentration dropped by half at the first CVVHDF and decreased obviously after two HPs. After stable observation in five days’ course of disease, the blood concentration was maintained at a low level and the patient was cured and discharged. Conclusion The implementation of the blood purification program under the monitoring of the blood drug concentration with the participation of pharmacists is helpful for the rescue of drug overdose and is worthy of promotion.
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Tacrolimus (Tac) is a commonly used immunosuppressant after organ transplantation, which has high immunosuppressive efficacy. However, the pharmacokinetics of Tac significantly differ among individuals, and gene polymorphism is the main influencing factor. In recent years, the gene polymorphism of drug transporter has become a novel research hotspot. Nevertheless, the effect of the gene polymorphism of transporter on Tac pharmacokinetics remains controversial. Consequently, the correlation between the gene polymorphism of transporter and Tac blood concentration plays a significant role in guiding Tac-based individualized immunosuppressive therapy. In this article, the research progresses on the gene polymorphism of adenosine triphosphate-binding cassette (ABC) transporter and solute carrier (SLC) transporter in organ transplantation was reviewed. The correlation between the gene polymorphism of transporter and Tac blood concentration was summarized, aiming to provide reference for Tac-based individualized therapy.
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Objective: To analyze the correlation between HD-MTX blood concentration and acute drug-induced liver and kidney injury in the patients with osteosarcoma, and investigate the significance of HD-MTX concentration in the monitoring of liver and kidney toxicity. Methods: A total of 56 osteosarcoma patients treated with HD-MTX were selected, and after HD-MTX treatment, the blood concentration of MTX was detected by an HPLC-UV method in 48 h and 72 h after the administration. The liver and kidney function were measured at the same time. The correlation between the different concentrations of MTX and the change of liver and kidney func-tion was analyzed. Results: All the patients were monitored MTX blood concentration at different time points. After the 48-hour HD-MTX treatment, 4 patients (7. 14% ) were with acute drug-induced liver injury and 13 patients (23. 21% ) showed drug-induced kid-ney injury. The average C48hof liver injury was (2.90 ±0.78) μmol·L-1, and the average C48hof kidney injury was (1.65 ±1.12) μmol·L-1. After the 72-hour HD-MTX treatment, 7 patients ( 12. 50% ) were with drug-induced liver injury and 16 patients (28.57%) showed drug-induced kidney injury. The average C72hof liver injury was (0.30 ±0.17) μmol·L-1, while the average C48hof kidney injury was (0. 29 ± 0. 29) μmol·L-1. The function indices of liver ( ALT, ALP and TBIL) and kidney ( SCr) were significantly higher than those in the normal group (P<0. 05), and the blood concentration of MTX was partly significantly correlated with those indicators. Conclusion: There is a certain correlation between MTX induced injury and the blood drug concentration at par-ticular points, and C48hmay be more valuable to predict drug-induced liver and kidney injury.
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Objective To investigate the comparation of sodium valproate concentration in peripheral blood monitoring by fluorescence polarization immunoassay method(FPIA)and high performance liquid chromatography method(HPLC)in epilepsy children.Methods 87 cases of epilepsy children received Sodium valproate treatment in our hospital from February 2014 to June 2016 were selected,fasting venous blood of elbow vein were collected the next morning after last medication, blood concentrations of Sodium valproate in serum samples were detected by FPIA method and HPLC method respectively,the correlation and consistency of results of the two methods were observed and compared.Results The intra day and inter day RSD of Sodium valproate concentration in peripheral blood in epilepsy children detected by FPIA were <5%,the recovery rate was 90%-110%,the precision and accuracy were high;The intra day and inter day RSD of Sodium valproate concentration in peripheral blood in epilepsy children detected by HPLC were <5%,the recovery rate was 90%-110%,the precision and accuracy were high; the linear regression equation between determination value of HPLC method (X) and determination value of FPIA method (Y) was:Y=0.8355X+1.8231,correlation coefficient r=0.914,the detection results were positively related;the Sodium valproate blood concentration detected by FPIA was significantly lower than that detected by HPLC method, the difference was statistically significant (P<0.05);Bland-Altman deviation chart results show that determination of blood drug concentration by HPLC method was higher than that of FPIA method by 7.2μg/mL.Conclusion The precision and accuracy of sodium valproate concentration in peripheral blood monitoring by FPIA method and HPLC method were all high, and the correlation was good, but the detection results of the two methods were significantly different,the detection result of HPLC method was higher than that of FPIA method,need to choose and judge according to the clinical situation.
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Objective:To analyze the correlation between cyclosporin A blood concentration and drug-induced liver and kidney in-jury in the patients with aplastic anemia, investigate the significance of cyclosporin A concentration in the monitoring of liver and kidney toxicity, and provide theoretical basis for clinical individualized drug use. Methods:A total of 149 patients with aplastic anemia trea-ted with cyclosporin A as the main therapeutic drug were selected, and after 3-day treatment, the blood concentration of cyclosporin A was detected by an HPLC-UV method 10 minutes before the administration and 2 hours after the administration. The liver and kidney function were measured at the same time. The correlation between the different concentration of cyclosporine A and the change of liver and kidney function was analyzed. Results:All the patients were monitored cyclosporine A blood concentration with 1236 samples, and 34 patients (22. 82%) were with drug-induced liver injury and 51 patients (34. 23%) showed drug-induced kidney toxicity. The average C0 of liver injury patients was (297. 92 ± 74. 14) μg·L-1 , and C2 was (944. 47 ± 148. 47) μg·L-1 , while the average C0 of kidney injury patients was (311. 41 ± 52. 80)μg·L-1, and C2 was (926. 25 ± 136. 02) μg·L-1. The function indices of liver (ALT, AST, TBIL) and kidney (SC, BUN, UA) were significantly higher than those in the normal group (P<0. 05), and the blood concentration of cyclosporin A was significantly correlated with the liver,and kidney function. Conclusion:There is a certain correla-tion between cyclosporine A -induced toxicity and its blood concentration and C2 may be a more valuable predictor for drug -induced liver injury.
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OBJECTIVE: To assess the influence of Qingdu (QD) capsule on the pharmacokinetic of HAART. METHODS: The 36 SD rats were divided into 3 groups. Rats in Group HAART were given, using an intragastric gavage needle, highly active antiretroviral therapy (HAART) containing zidovudine (AZT), 2',3'-dideoxy-3'-thiacytidine (3TC) and efavirenz (EFV). Group HAART+QD were given HAART and QD capsule simultaneously. Group HAART+QD (2 h interval) were given HAART and then given QD capsule 2 h later. Blood samples were collected at 0, 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 h. AZT, 3TC, and EFV concentrations were tested with high performapce liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Pharmacokinetic parameters were compared among different groups. RESULTS: The t1/2 of AZT were statistically different among the three groups (P<0.05), Group HAART+QD (2 h interval) had the lease t1/2 of AZT than the other two groups. There were no statistical differences among groups for the AUC0-12, tmax, ρmax and CL of AZT, and all five parameters of 3TC and EFV. CONCLUSION: QU doesn't show influence on pharmacokinetic parameters of AZT+3TC+EFV regimen, but intention should be paid to individual differences.
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Objective To study the blood concentration of hydroxychloroquine in patients with systemic lupus erythematosus (SLE) treated with different doses, and analyze the relationship between blood concentration of hydroxychloroquine and disease activity, and evaluate its safety.Methods Forty SLE patients were randomly divided into 2 groups, each group contained 20 cases.The patients in group A were treated with hydroxychloroquine (0.4 g, qd), while patients in group B were treated with hydroxychloroquine (0.2 g, qd).The treatment lasted more than six months in every patient.The blood concentrations of hydroxychloro-quine were detected by high performance liquid chromatography.The clinical and laboratory indices were collected.The systemic lupus erythematosus disease activity index (SLEDAI) score was recorded.The doses and varieties of combined hormone, immunosuppressant were recorded.The correlation of blood concentration of hydroxychloroquine and disease activity was analyzed.The significance was determined by Student's t test and Pearson correlation analysis.Results In SLE patients, the average blood concentration of hydro-xychloroquine was (402±190) ng/ml in group A and (150±60) ng/ml in group B (t=7.471, P＜0.01).The disease activities of patients in the two groups showed no significant difference (t=-0.172, P＞0.05).The platelet counts of patients in group A were significantly higher than those in group B[(188±88)×109/L vs (158 ±87) ×109/L] (t=4.375, P＜0.05).However, the other laboratory parameters showed no significant difference between the two groups (P＞0.05).Conclusion The results of this study indicate that the blood concentrations of hydroxy-chloroquine are significantly different in different dosages.The high dose of hydroxy-chloroquine is related to high platelet number in lupus patients.These findings suggest that hydroxychloroquine is safe and effective for SLE patients.
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Objective This study was designed to validate the utility of a population pharmacokinetic model established for vancomycin in patients with severe neurosurgical disease . Methods The clinical data including patient gender , age , body weight ,serum creatinine and albumin were collected retrospectively from patients in Nanjing Drum Tower Hospital to calculate the steady trough concentration of vancomycin using the previously established pharmacokinetic model .The predicted value was compared with the actual value .Results During the period from March 2013 to March 2014 ,53 blood samples with serum trough concentration of vancomycin were collected from 42 patients .The average trough concentration of vancomycin was 10 .9 mg/L (range from 1 .6 to 49 .1 mg/L) .The predicted trough level of vancomycin based on the population pharmacokinetic model was significantly correlated to the actual value(r=0 .857 ,P<0 .001) .The mean absolute percentage error was 0 .407 9 . The confidence interval was 9 .36‐14 .07 for the predicted values ,and 8 .92‐14 .32 for the actual values .Conclusions The pharmacokinetic model is valid and useful for planning intravenous dose of vancomycin in patients with severe neurosurgical disease .Large error (about 30% ) was observed in estimation of body weight due to coma .Reduced renal function following contrast agent and/or diuretic drug has an impact on the predicted results . The accuracy of prediction can be increased to nearly 70% after adjusting the covariates .
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Objective To study the correlation of blood drug concentration determination of sodium valproate in children with epilepsy by using enzyme-multiplied immunoassay test (EMIT) and high performance liquid chromatography (HPLC), so as to provide basis of selection in clinical determination of sodium valproate ( VPA) .Methods 200 blood samples of epileptic children taking sodium valproate were collected, blood concentration were determined by EMIT and HPLC method, and the correlation was analyzed.Results The following regression equation was obtained by determination results of HPLC (X) and EMIT (Y): Y=1063.517X-331.351(r=0.933), which had significant correlation (P<0.05).The plasma concentration of VPA determined by EMIT was higher than that by HPLC.Conclusion The determination results of VPA concentration in epileptic children by using EMIT and HPLC has significant correlation, and it should choose the suitable method to determine the blood drug concentration of VPA based on the actual situation.
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Objective To analyze if the increasing the dose and time of vancomycin will increase the renal toxicity risk in patients with resistance to toluene penicillin Staphylococcus aureus (methicillin-resistant Staphylococcus aureus, MRSA) and blood drug concentration significance in the course of treatment.Methods We enrolled 105 patients, mean age (58.0 ±5.8) years;59 males (61.9%) treated in our hospital with MRSA.Patients’ age, sex, serum creatinine (SCr), creatinine clearance rate (CrCl), serum vancomycin concentrations, duration of treatment, acute physiology and chronic health evaluation II score were analysed.The definition of renal toxicity is that SCr is higher than the baseline 0.5 mg/dL, or according to the measurement results of a series SCr:SCr elevation≥50%.The relevant data in patients with renal toxicity and non toxicity were compared.Results 45 (42.9%) had renal toxicity.Vancomycin concentration was significantly higher in renal toxicity patients than non toxicity [(20.9 ±9.8)μg/mL vs. (14.2 ±6.6)μg/mL, P<0.001), serum drug concentration≥15μg/mL (67.8% vs 40.3%; P =0.01) and vancomycin treatment duration (14 days) ( 46.0% vs 21.4%; P =0.011 ) has obvious different scale between two groups. Regression analysis showed that: vancomycin serum concentration≥15μg/mL and prolonged treatment were independent predictors of renal toxicity ( adjusted likelihood ratio =2.83; 95%CI, 1.03 ~7.72, P=0.045).Conclusion The increase of vancomycin dosage and treatment time was the risk of nephrotoxicity.
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Objective: To compare the in vivo pharmacokinetic properties of Kushenin Injection Nanoparticles (KU-PLGA-NS) with the ordinary Kushenin Injection (KUI) of rats. Methods: A method has been developed and validated for the quantification of kushenin in rat plasma. Using ANOVA method to choose the compartment model, The plasma concentration-time data were measured and then analyzed by DAS program on the computer. According to F values, the AIC choice compartment model pharmacokinetic parameters were calculated. Results: The main pharmacokinetic parameters of KU-PLGA-NS and KUI were as follows: AUC 0-t, were (785.57±170.92) and (342.43±54.49) mg·L-1·min, respeticevly; Cmax were (18.51±2.47) and (28.48±5.40) mg/L, respeticevly; t 1/2Ke were (91.69±1.94) and (11.51±2.47) min, respeticevly. Conclusion: Comparison of in vivo pharmacokinetic characteristics of rats between KU-PLGA-NS and KUI has a significant change with AUC and C max increase and t1/2 extension.
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OBJECTIVE:To establish a HPLC-fluorescence detection method for the determiniation of the serum concentration of metoprolol.METHODS:The determination was performed on Symmetry C18 column,and the mobile phase consisted of acetonitrile-water-triethylamine -phosphoric acid(110∶390∶2.5∶1.6) at a flow rate of 0.8 mL?min-1.The excitation wavelength was 265 nm and the emission wavelength 298 nm,and the sample size was 20 ?L.RESULTS:Good linearity was obtained for metoprolol over the range of 2.0～100.0 ?g?L-1 with correlation coefficient r=0.999 6.At low,medium and high concentrations,the average recoveries of metoprolol were 99.73%,98.21% and 99.38%,respectively.The intra-day RSD were 2.89%,2.36% and 1.32%,respectively,and the inter-day RSD were 3.73%,3.03% and 2.25% respectively.The lowest detectable limit was 1.0 ?g?L-1.CONCLUSION:This method is precise,accurate,specific,simple yet with high recovery,and it is applicable for clinical monitoring of blood concentration and pharmacokinetic study.
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0.05) between in 2 groups.CONCLUSION: Used in combination with rifampin,bicyclol showed insignificant effect on the pharmacokinetics of rifampin in rats.
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OBJECTIVE:To establish a RP-HPLC method to determinate the plasma concentration of paclitaxel in tumor patients.METHODS:Paclitaxel was extracted from plasma with organic phase(ethyl-acetate)by two-step extraction on Tianhe Kromasil C18 column(250 mm?4.6 mm,5 ?m)with a mobile phase consisted of acetonitrile-methanol-water(40∶25∶40)at a flow rate of 1 mL?min-1.The detective wavelength was set at 227 nm and the column temperature was maintained at 35 ℃.RESULTS:The linear range of paclitaxel was 0.05～5.00 mg?L-1(r=0.999 7)with average recovery rate at 98.75%～100.44%.Both intra-day RSD and inter-day RSD were less than 5%(n=5).The plasma concentration-time profile in 11 patients after iv infusion of paclitaxel was in line with a two-compartment model.CONCLUSION:This established method is simple,accurate,reproducible and applicable for clinical determination of blood drug concentration and pharmacokinetic studies.
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OBJECTIVE:To establish an HPLC-CSP (chiral stationary phase) for the determination of plasma levels of enantiomers of fluoxetine. METHODS: Enantiomers of fluoxetine were separated on a Chirobiotic V column. The mobile phase consisted of methanol-acetic acid-triethylamine (100∶0.04∶0.04) with a flow rate of 1 mL?min-1. The detection wavelength was set at 226 nm.Clozapine was used as the internal standard. RESULTS: Under this chromatographic condition, both R-norfluoxetine and S-norfluoxetine had no interference on the enantiomers of fluoxetine and the internal standard. The calibration curve was linear in the range of 8.1～432 ng?mL-1(r=0.999 8) for R-enantiomer and in the range of 10.8～432 ng?mL-1 (r=0.999 2) for S-enantiomer. The relative recovery of R-fluoxetine and S-fluoxetine in plasma were 97.2%～101.9% and 98.7%～102.2%, respectively. RSD of intraday and interday ranged from 2.6% to 5.3% and from 7.7% to 8.9% for R-fluoxetine, and from 2.1% to 6.7% and from 8.0% to 10.6% for S-fuoxetine, respectively. CONCLUSION: The method is simple, reliable and sensitive, and applicable for the determination and pharmacokinetic study of the enantiomers of fluoxetine in plasma.
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OBJECTIVE:To establish a RP-HPLC method for simultaneous determination of caffine,acetaminophen and isopropylphenazone in human plasma after oral dose of saridon.METHODS:Hypersil Hypurity TM Advance was used as chromatographic column and the mobile phase was a mixture of0.01mol/L phosphoric acid-methanol-tetrahydrofuran(86∶12∶2).The detection wavelength was273nm.RESULTS:The calibration curves were linear in the ranges of0.39～100.0?g/ml for caffine,1.96～500.0?g/ml for acetaminophen,and1.17～300.0?g/ml for isopropylphenazone,respectively.The accuracy of all was higher than95.0%.The inter-day and intra-day RSD was less than10.0%.CONCLUSION:The present method is sensitive,accurate,convenient,and highly specific,which can meet the requirement in plasma determination of three components in Saridon tablet.
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Objective To explore the blood drug concentration monitoring of sustained-release valproate(DK)in children with epilepsy,focusing on the selection of sampling time and evaluation of the results.Methods Two hundred and seventy-one children taking DK and 155 children taking sodium valproate syrup(VPA Syr)were involved and their serum were taken when achieved steady state to determine the valproic acid level using fluorescence polarization immunoassay.They were divided into 4 groups,which were DK taken once daily group(DK qd group,126 children),DK taken once daily at night and sampled on morning group(DK qn group,26 children),DK taken every 12 h group(DK q12 h group,119 children),VPA Syr q12 h group(155 children).Determine the proportion of the blood drug concentration of each group below,ithin and above the therapeutic range for valproate(50-100 mg/L)were determined.The data were analyzed by t test.Results The Cmin of DK qd group were(73.09?19.91)mg/L,significantly lower from the serum concentration of DK qn and sampled on morning group [(94.94?25.44)mg/L](P0.05).Conclusions DK qn should sampled at night before the night dose.The Cmin of DK q12 h was higher according to the therapeutic range,it's favorable range still needs clinical practice.
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Objective To provide an information monitoring software for therapy drug,which can automatically construct safe concentration scope,statistically analyses data,query and input data.Methods TDMIS is developed by Powerbuilder 9.0 and is run in WIN 98 or the copy over it.2062 cases are analyzed through TDMIS and a safe concentration scope is set.Conclusion TDMIS is a practical software.It can make drug prescription standardized,computerized and easy to be statistically analyzed.The working efficiency and quality of clinical apothecary are greatly improved.
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OBJECTIVE:To study the optimal monitoring indexes of plasma concentration of cyclosporine A(CsA) in patients receiving hematopoietic stem cell transplantation.METHODS:The lowest CsA concentration(C0) and the highest CsA concentration(C2) in 23 hematopoietic stem cell transplant recipients were detected by FPIA.All the data were analyzed statistically.RESULTS:Within 6 months after hematopoietic stem cell transplanttion,C0,C2,C0+C2 and C2/C0 in the recipients were(228.84?142.48) ?g?L-1,(741.50?294.42) ?g?L-1,(970.34?391.18) ?g?L-1 and(3.88?1.94) ?g?L-1,respectively.CONCLUSION:As reasonable monitoring indexes for the plasma concentration of CsA,C0+C2 and C2/C0 can comprehensively reflect the exposure of drug in body and monitor the toxicity of CsA in liver and kidney.