Simultaneous determination of metolazone and valsartan in plasma by on-line SPE coupled with liquid chromatography/tandem mass spectrometry

Zhou, Jiezhao; Chen, Mei‐Ling; Liu, Ying; Yu, Fanglin; Cheng, Xiaohui; Yang, Yang; Liu, Yan; Xie, Xiangyang; Li, Zhiping; Zhang, Hui; Mei, Xingguo

doi:10.1177/1469066717716726

Cited by 5 publications

(2 citation statements)

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“…The liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis method of ropivacaine was optimized on the basis of previous reports [28][29][30]. The liquid chromatography analysis conditions are shown in Table 2, including a column temperature of 20˚C, injection volume of 10 μL, flow rate of 0.40 mL�min -1 , and sample chamber temperature of 2~8˚C.…”

Section: Pharmacokineticsmentioning

confidence: 99%

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A randomized trial: The safety, pharmacokinetics and preliminary pharmacodynamics of ropivacaine oil delivery depot in healthy subjects

Lu,

Zhao,

Wang

et al. 2023

PLoS ONE

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Introduction Ropivacaine oil delivery depot (RODD) can slowly release ropivacaine and block nerves for a long timejavascript:;. The aim of the present work was to investigate the safety, pharmacokinetics, and preliminary pharmacodynamics of RODD in subcutaneous injection among healthy subjects. Methods The abdomens of 3 subjects were subcutaneously administered with a single-needle RODD containing 12~30 mg of ropivacaine. The irritation, nerve blocking range and optimum dose were investigated. Forty-one subjects were divided into RODD groups containing 150, 230, 300, 350 and 400 mg of ropivacaine and a ropivacaine hydrochloride injection (RHI) 150 mg group. Multineedle subcutaneous injection of RODD or RHI was performed in the abdomens of the subjects. The primary endpoint was a safe dose or a maximum dose of ropivacaine (400 mg). Subjects’ vital signs were observed; their blood was analyzed; their cardiovascular system and nervous systems were monitored, and their dermatological reactions were observed and scored. Second, the ropivacaine concentrations in plasma were determined, pharmacokinetic parameters were calculated, and the anesthetic effects of RODD were studied, including RODD onset time, duration and intensity of nerve block. Results Single-needle injection of RODD 24 mg was optimal for 3 subjects, and the range of nerve block was 42.5±20.8 mm. Multineedle subcutaneous injection of RODD in the abdomens of subjects was safe, and all adverse events were no more severe than grade II. The incidence rate of grade II adverse events, such as pain, and abnormal ST and ST-T segment changes on electrocardiography, was approximately 1%. The incidence rate of grade I adverse events, including erythema, papules, hypertriglyceridemia, and hypotension was greater than 10%. Erythema and papules were relieved after 24 h and disappeared after 72 h. Other adverse reactions disappeared after 7 days. The curve of ropivacaine concentration-time in plasma presented a bimodal profile. The results showed that ropivacaine was slowly released from the RODD. Compared with the 150 mg RHI group, Tmax was longer in the RODD groups. In particular, Tmax in the 400 mg RODD group was longer than that in the RHI group (11.8±4.6 h vs. 0.77±0.06 h). The Cmax in the 150 mg RODD group was lower than that in the 150 mg RHI group (0.35±0.09 vs. 0.58±0.13 μg·mL-1). In particular, the Cmax increased by 48% when the dose was increased by 2.6 times in the 400 mg group. Cmax, the AUC value and the intensity of the nerve block increased with increasing doses of RODD. Among them, the 400 mg RODD group presented the strongest nerve block (the percentage of level 2 and 3, 42.9%). The corresponding median onset time was 0.42 h, and the duration median was 35.7⁓47.7 h. Conclusions RODD has a sustained release effect. Compared with the RHI group, Tmax was delayed in the RODD groups, and the duration of nerve block was long. No abnormal reaction was found in the RODD group containing 400 mg of ropivacaine after subcutaneous injection among healthy subjects, suggesting that RODD was adequately safe. Trial registration Chictr.org: CTR2200058122; Chinadrugtrials.org: CTR20192280.

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Section: Pharmacokineticsmentioning

confidence: 99%

“…The extraction and detection method were verified, and the content of ropivacaine in plasma samples was determined. At 0.25 h before and 0.5, 1, 1 5,2,4,6,8,10,12,14,21,24,27,30,33,36…”

mentioning

confidence: 99%