RESUMEN
BACKGROUND: The investigation of drug disposition in tissues is critical to improving dosing strategy and maximizing treatment effectiveness, yet developing a multi-tissue bioanalytical method could be challenging due to the differences among various matrices. Herein, we developed an LC-MS/MS method tailored for the quantitation of piperacillin (PIP), cefazolin (CFZ), and cefoxitin (CFX) in rat plasma and 12 tissues, accompanied by validation data for each matrix according to the FDA and EMA guidelines. RESULTS: The method required only a small sample volume (5⯵L plasma or 50-100⯵L tissue homogenates) and a relatively simple protocol for simultaneous quantitation of PIP, CFZ, and CFX within different biological matrices. Mobile phase A was composed of 5â¯mM ammonium formate and 0.1â¯% formic acid in water, while mobile phase B contained 0.1â¯% formic acid in acetonitrile. The mobile phase was pumped through a Synergi Fusion-RP column equipped with a guard column with a gradient elution program at a 0.3â¯mL/min flow rate. The mass spectrometer was operated in positive ionization mode (ESI+) using multiple reaction monitoring. SIGNIFICANCE: The validated method has been successfully applied to quantify PIP, CFZ, and CFX from the plasma and tissue samples collected in a pilot rat study and will further be used in a large pharmacokinetic study. To our knowledge, this is also the first report presenting long-term, freeze-thaw, and autosampler stability data for PIP, CFZ, and CFX in rat plasma and multiple tissues.
Asunto(s)
Cefazolina , Cefoxitina , Piperacilina , Espectrometría de Masas en Tándem , Animales , Espectrometría de Masas en Tándem/métodos , Ratas , Cefazolina/sangre , Cefazolina/farmacocinética , Cefazolina/análisis , Piperacilina/sangre , Piperacilina/farmacocinética , Piperacilina/análisis , Cefoxitina/farmacocinética , Cefoxitina/sangre , Cefoxitina/química , Cefoxitina/análisis , Cromatografía Liquida/métodos , Reproducibilidad de los Resultados , Distribución Tisular , Ratas Sprague-Dawley , Antibacterianos/sangre , Antibacterianos/farmacocinética , Antibacterianos/análisis , Masculino , Cromatografía Líquida con Espectrometría de MasasRESUMEN
OBJECTIVE@#To observe the therapeutic effect of acupuncture combined with western conventional therapy on type Ⅱ respiratory failure of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and evaluate the effect of acupuncture on diaphragmatic function and prognosis by bedside ultrasound.@*METHODS@#A total of 111 patients with AECOPD type Ⅱ respiratory failure were randomized into an acupuncture group, a conventional treatment group and a non-acupoint acupuncture group, 37 cases in each one. The routine AECOPD nursing care and treatment with western medicine were provided in the 3 groups. Additionally, in the acupuncture group, acupuncture was applied at Dingchuan (EX-B 1), Feishu (BL 13), Taiyuan (LU 9), Danzhong (CV 17) and Zhongwan (CV 12), etc. In the non-acupoint acupuncture group, acupuncture was given at the points 5 to 10 mm lateral to each of the acupoints selected in the acupuncture group. Acupuncture was given once every day, 30 min each time, consecutively for 10 days in the above two groups. Separately, before treatment, on day 3, 7 and 10 of treatment, arterial partial pressure of oxygen (PaO@*RESULTS@#On day 3, 7 and 10 of treatment, PaO@*CONCLUSION@#Acupuncture as adjunctive therapy achieves significant therapeutic effect on AECOPD type Ⅱ respiratory failure. It improves diaphragmatic function, promotes oxygenation and relieves carbon dioxide retention of artery, alleviates clinical symptoms and reduces the time of mechanic ventilation and hospitalization. Besides, the bedside ultrasound detection can objectively reflect the effect of acupuncture on diaphragmatic function in the patients with AECOPD complicated with typeⅡrespiratory failure.
Asunto(s)
Humanos , Puntos de Acupuntura , Terapia por Acupuntura , Diafragma , Enfermedad Pulmonar Obstructiva Crónica/terapia , Insuficiencia Respiratoria/terapiaRESUMEN
OBJECTIVE@#To observe the analgesic and sedative effects of acupuncture in elderly patients with severe pneumonia during invasive mechanical ventilation.@*METHODS@#A total of 188 elderly patients with severe pneumonia were randomly divided into an observation group and a control group, 94 cases in each group. Both groups were treated with routine nursing and treatment of severe pneumonia such as invasive mechanical ventilation, analgesia and sedation. Based on these, the observation group was treated with acupuncture at Neiguan (PC 6), Hegu (LI 4), Yintang (GV 29) and Baihui (GV 20), twice a day until the mechanical ventilation was offline. The critical care pain observation tool (CPOT) score and Richmond agitation-sedation score (RASS) were observed before treatment and 0.5 h after analgesia and sedation; the average time of reaching the standard, the reaching standard rate of shallow sedation and analgesia within 0.5 h and 72 h as well as the dosage of analgesic and sedative drugs and compilations were compared between the two groups. The mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR) and blood oxygen saturation (SpO@*RESULTS@#At the time point of 0.5 h after treatment, the CPOT and RASS scores in the two groups were lower than those before treatment (@*CONCLUSION@#Acupuncture has analgesic and sedative effect in elderly patients with severe pneumonia during invasive mechanical ventilation, which could reduce the dosage of sedative and analgesic drugs and the occurrence of complications, improve blood oxygen, and has good safety.