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OBJECTIVE：To establish a method for the determination of pyrrotinib concentration in plasma ，and apply it in clinic. METHODS ：After precipitated with methanol ，the plasma sample was determined by LC-MS/MS using imatinib as internal standard. The determination was performed on Ultimate AQ-C 18 column with mobile phase consisted of methanol （containing 0.1％ formic acid ）and water （containing 0.1％ formic acid ）（gradient elution ）at the flow rate of 0.4 mL/min. The column temperature was 40 ℃，and the sample size was 5 µL. The ion source was electrospray ionization source ，and the positive ion scanning was carried out in multiple reaction mode. The ion pairs for quantitative analysis were m/z 583.4→138.3（pyrrotinib）and m/z 494.5→ 393.4（internal standard ），respectively. Thirty breast cancer patients taking pyrrotinib were collected from the Affiliated Hospital of Qingdao University during Jun.-Nov. 2020 to determine their steady-state trough concentrations of pyrrotinib after a week of treatment. RESULTS ：The linear range of pyrrotinib were 5-300 ng/mL（r＝0.999 3）. The lower limit of quantification was 5 ng/mL. RSDs of intra-day and inter-day were not higher than 9.30％，and relative errors （REs）ranged －6.70％-5.04％. REs of stability tests were in the range of －1.92％-5.42％. The extraction method ，matrix effect and residual effect did not affect the quantitative analysis of the substance to be tested. The steady-state trough concentrations of pyrrotinib were 32.6-82.8 ng/mL，with an average plasma concentration of 53.8 ng/mL；there was about 2.54 fold individual difference. CONCLUSIONS ：Established LC-MS/MS method is simple ，sensitive and accurate ，and can be used for the plasma concentration monitoring of pyrrotinib in breast cancer patient.
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AIM: To evaluate relationship between dosing schedules and safety of voriconazole by analyzing the monitoring results of voriconazole in patients with liver dysfunction, and to provide reference for the clinical individualized medication. METHODS: The blood concentration and safety information of voriconazole in patients with liver dysfunction was searched in PubMed, Cochrane Library, Wanfang, Weipu, and Chinese Journal Full-text Database from the establishment of the databases to December 2019, the dosing schedule and safety range of voriconazole for patients with liver dysfunction was analyzed. RESULTS: A total of 10 literatures were selected, 5 of which were multi-sample retrospective studies and 1 of which was prospective study, and the remaining 4 were case reports. In Child-Pugh grade C liver dysfunction, a maintenance dose of 100 mg q12h is more secure. The incidence of adverse reactions of voriconazole is generally within 7 days. When the target trough concentration is less than 5 mg/L or 5.3 mg/L, the incidence of adverse reactions is still high. The main adverse reactions include neurotoxicity, hallucinations, visual disturbances, gastrointestinal reactions and rash. CONCLUSION: The dose of voriconazole in patients with liver dysfunction should be reduced, and the drug concentration should be monitored in a timely manner. It is recommended that on the basis of ensuring the efficacy, trough concentration can be further reduced to reduce the occurrence of adverse reactions in patients with liver dysfunction.
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Objective: To monitor vancomycin plasma concentration results by clinical pharmacists in order to participate in individualized medication adjustment.Methods: Clinical pharmacist monitored the blood concentration of vancomycin in special patients, and then designed the individualized medication according to the monitoring results and clinical manifestations of patients.Results: Through the individualized medication adjustment, clinical pharmacist enhanced the efficacy and reduced the incidence of adverse reactions, and improved the level of clinical rational drug use as well.Conclusion: Clinical pharmacist can provide better service for clinics through the practice of individualized precision pharmacy, and reasonable and safe pharmacy service can be provided for patients.
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Objective To establish a rapid LC-MS/MS method for the simultaneous quantitative determination of lopinavir (LPV)and ritonavir(RTV)in human plasma. Methods Plasma samples were prepared by protein precipitation and separated by a Thermo Hypersil GOLD column(2.1 mm×100 mm,5 mm)with the mobile phase consisting of methanol and water(0.1%formic acid) at a flow rate of 0.2 ml/min. Detection of LPV,RTV and the internal standard(IS)MS 275 was performed using selected reaction moni?toring(SRM)of the transitions m/z 629.3→155.0,m/z 721.3→268.0 and m/z 377.1→359.2 in positive ion mode,respectively. Re?sults The calibration curve was linear in the range of 20-1000 ng/ml(r>0.994)for LPV and RTV. The intra and inter-day precision and accuracy values met the set acceptance criteria. Conclusion The method is rapid,sensitive and accurate for the therapeutic drug monitoring of LPV and RTV simultaneously in clinic and pharmacokinetic studies.
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Objective To establish a rapid LC- MS/MS method for the simultaneous quantitative determination of lopinavir (LPV) and ritonavir (RTV) in human plasma. Methods Plasma samples were prepared by protein precipitation and separated by a Thermo Hypersil GOLD column (2.1 mm×100 mm, 5 mm) with the mobile phase consisting of methanol and water (0.1% formic acid) at a flow rate of 0.2 ml/min. Detection of LPV, RTV and the internal standard (IS) MS 275 was performed using selected reaction moni-toring (SRM) of the transitions m/z 629.3→155.0, m/z 721.3→268.0 and m/z 377.1→359.2 in positive ion mode, respectively. Re-sults The calibration curve was linear in the range of 20-1000 ng/ml (r0.994) for LPV and RTV. The intra and inter-day precision and accuracy values met the set acceptance criteria. Conclusion The method is rapid, sensitive and accurate for the therapeutic drug monitoring of LPV and RTV simultaneously in clinic and pharmacokinetic studies.
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Objective To discuss the clinical significance of vancomycin plasma concentration monitoring and its relationship with adverse reactions in treatment of elderly patients. Methods The clinical records of 32 patients aged over 70 years admitted in the Emergency Medical Department of Sichuan Provincial People's Hospital were collected. Based on the diagnosis and laboratory examinations on admission, the patients were treated with cefoperazone+sulbactam or moxifloxacin, while in patients with severe infections, intravenous drip of carbapenem antibacterial drugs were given. After treatment for 3-5 days, when no effective results were obtained, according to the pathogenic results achieved from cultures of blood, sputum, secretions, catheter, etc, the corresponding treatment was given. If the infection was caused by positive bacteria mainly methicillin-resistant Staphylococcus aureus (MRSA) sensitive to vancomycin, the original antibiotic was replaced by vancomycin or vancomycin combined with other antibiotic; intravenous drip of vancomycin 1 g in 250 mL normal saline was given, once in 12 hours, with a speed of 10 mg/min or not over 15 mg/min. The function of liver and kidney, and auditory impairment were observed, and the correlation between vancomycin plasma concentration and adverse reactions was analyzed. Results The total incidence of adverse reactions in elderly patients with different serum vancomycin trough concentrations was 37.50%(12/32) in which the highest incidence was kidney damage 18.75%(6/32) followed by the hearing loss 9.38%(3/32) and liver damage 9.38%(3/32). There were no statistical significant differences in the rates of adverse reactions among the different vancomycin trough concentrations (20 mg/L) and [37.50%(6/16), 38.46%(5/13), 33.33%(1/3), all P>0.05], that meant along with the increase of vancomycin concentration, no tendency of increment of adverse reactions was seen. Of the 32 cases, there were 13 treated by vancomycin combined with other antibiotic, the combination rate being 40.63%. There were 2 cases of hepatic impairment (11.83%), 1 case of renal impairment (7.69%) and none hearing damage in patients treated with combination of antibiotic therapy. Therefore no correlation was concluded between the occurrence of adverse reactions and the combination therapy ( r=0.15, P>0.05). Conclusions In elderly patients over the age of 70 years, there is a higher incidence of kidney damage in the application of vancomycin. Thus, the monitoring of vancomycin plasma concentration in elderly patients has instructive significance in its clinical use.