Quantification of acyclovir in dermal interstitial fluid and human serum by ultra‐high‐performance liquid–high‐resolution tandem mass spectrometry for topical bioequivalence evaluation

Schimek, Denise; Raml, Reingard; Francesconi, Kevin A.; Bodenlenz, Manfred; Sinner, Frank

doi:10.1002/bmc.4194

Cited by 11 publications

(12 citation statements)

References 23 publications

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“…In our study, we investigated the RR and AR of six recombinant human cytokines of increasing molecular size using in vitro, ex vivo, and in vivo experiments. Due to their similarities to interstitial fluid and human skin [ 36 , 37 ], we used human serum and porcine skin, respectively, ex vivo and in vivo. Finally, we used excised human skin ex vivo and in vivo to find the most efficient perfusate (crystalloid or colloids) for investigating intercellular signalling in clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…The membrane and catheter were placed in syringes that were containing either Ringer’s lactate or human serum, which was chosen to mimic the interstitial fluid that surrounds the membrane when placed in living tissue. Although not identical, human serum is quite similar to interstitial fluid [ 36 , 37 ]. Furthermore, for the in vivo analysis, we subjected human and porcine skin cadavers and porcine dermal skin from anaesthetized domestic pigs to retrodialysis (i.e., inverse microdialysis).…”

Section: Introductionmentioning

confidence: 99%

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Cytokine and Chemokine Recovery Is Increased by Colloid Perfusates during Dermal Microdialysis

et al. 2018

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Cytokines and chemokines play important roles in cell signalling, and microdialysis is a promising tool for monitoring these inflammation markers ex vivo. Therefore, the collecting of these mediators at the highest concentrations possible is crucial. Depending on the size of the mediator of interest, the collection of these high molecular mass molecules has thus far been difficult due to their low recovery, even when using high cut-off (100 kDa) microdialysis membranes. This study aimed to optimize the recovery of various cytokines and chemokines by validating the use of different perfusates in cutaneous microdialysis, and comparing intravenous (i.v.) colloids, crystalloids, and a lipid emulsion formulations that are approved for i.v. applications. Methods: In vitro and in vivo recovery experiments using six recombinant cytokines varying in molecular size (interleukin-2 (15 kDa), interleukin-6 (20.5 kDa), interleukin-8 (8 kDa), interleukin-12p70 (70 kDa), TNF-α (17.5 kDa), and vascular endothelial growth factor (VEGF) (38 kDa)) were performed in the presence of different perfusates for i.v. applications: Ringer’s lactate, dextran 60 kDa, hydroxyethyl starch 70 kDa, and hydroxyethyl starch 200 kDa solutions as well as a lipid emulsion formulation. Recovery was determined through (i) microdialysis of cytokines and chemokines in Ringer’s lactate solution or human serum in vitro, and (ii) retrodialysis of excised porcine and human skin cadavers in vitro and porcine skin in vivo. Furthermore, we used skin trauma (catheter insertion) and Ultraviolet B irradiation of 3 × 3 cm2 skin areas to sample cytokines and chemokines in vivo and compared the amounts that were obtained using crystalloid and colloid perfusates. All the cytokines and chemokines within the dialysates were quantified through a flow cytometry-based bead array assay. Results: Overall, recovery was strongly increased by the colloids, particularly hydroxyethyl starch 70 kDa, in vitro, ex vivo, and in vivo. When compared with the recovery achieved using Ringer’s lactate, this increase was most effective for proteins ranging from 8 to 20.5 kDa. Hydroxyethyl starch 70 kDa significantly increased the recovery of interleukin (IL)-8 in human serum in vitro when compared with Ringer’s lactate. More cytokines and chemokines were recovered using colloids compared with crystalloids. However, the increase in recovery values was lower for IL-12p70 and VEGF. Conclusions: Regarding the dialysate volumes and final dialysate concentrations, colloid perfusates are overall superior to crystalloid perfusates, such as Ringer’s lactate, when sampling cytokines and chemokines, resulting in higher recoveries. However, the sampling of high-molecular-mass cytokines during microdialysis remains challenging, and experimental in vitro data are not completely comparable with data obtained ex vivo or in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytokine and Chemokine Recovery Is Increased by Colloid Perfusates during Dermal Microdialysis

et al. 2018

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“…Highresolution mass spectrometry (HRMS) can not only accurately measure the mass of ions, but also determine their elemental (and isotopic) composition accurately. Ultra-highperformance liquid chromatography-high resolution tandem mass spectrometry (UHPLC-HR MS/MS) was used for introduced into the determination of ACV in human dermal interstitial fluid and serum form, as reported by Schimek et al [76]. They indicated that the concentration range was from 0.1 ng/mL to 25 ng/mL with a sample volume of only 20 µL and validated the successful application with short-term and long-term sample stability data and the analysis of 5000 clinical trial samples.…”

Section: Liquid Chromatography/tandem Mass Spectrometry (Lc-ms/ms)mentioning

confidence: 99%

Critical Review of Synthesis, Toxicology and Detection of Acyclovir

Wei

Yao

et al. 2021

Molecules

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Acyclovir (ACV) is an effective and selective antiviral drug, and the study of its toxicology and the use of appropriate detection techniques to control its toxicity at safe levels are extremely important for medicine efforts and human health. This review discusses the mechanism driving ACV’s ability to inhibit viral coding, starting from its development and pharmacology. A comprehensive summary of the existing preparation methods and synthetic materials, such as 5-aminoimidazole-4-carboxamide, guanine and its derivatives, and other purine derivatives, is presented to elucidate the preparation of ACV in detail. In addition, it presents valuable analytical procedures for the toxicological studies of ACV, which are essential for human use and dosing. Analytical methods, including spectrophotometry, high performance liquid chromatography (HPLC), liquid chromatography/tandem mass spectrometry (LC-MS/MS), electrochemical sensors, molecularly imprinted polymers (MIPs), and flow injection–chemiluminescence (FI-CL) are also highlighted. A brief description of the characteristics of each of these methods is also presented. Finally, insight is provided for the development of ACV to drive further innovation of ACV in pharmaceutical applications. This review provides a comprehensive summary of the past life and future challenges of ACV.

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“…Stability was tested only for the prepared serum samples, as the short-term and long-term stability of serum, plasma, and standard solutions has already been published. [2,10,12,15,16,21,28] The stability of prepared serum…”

Section: Stability Studiesmentioning

confidence: 99%

“…Chromatographic methods, namely, HPLC with UV light [3,4,[9][10][11][12][13] or fluorescence detection, have been developed [1,14,15]. More recent methods are based on UHPLC/MS/MS [16][17][18][19]. UHPLC/MS/MS separation using sub-2 μm particle columns offers improved specificity and sensitivity and can reduce separation time while maintaining separation efficiency [20].…”

Section: Introductionmentioning

confidence: 99%

Determination of acyclovir and its metabolite 9‐carboxymethoxymethylguanide in human serum by ultra‐high‐performance liquid chromatography‐tandem mass spectrometry

Urinovska

Kacířová

Sagan

2021

J of Separation Science

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A simple and rapid ultra‐high‐performance liquid chromatography coupled with mass spectrometry method was developed for acyclovir and its metabolite 9‐carboxymethoxymethylguanine in human serum. After precipitation of serum samples with 0.1% formic acid in acetonitrile/methanol (40:60, v/v), components were separated on a Luna Omega C18 column (1.6 μm; 2.1 × 150 mm) at 40°C. Mobile phase A (2 mmol/L ammonium acetate, 0.1% formic acid in 5% acetonitrile, v/v/v) and mobile phase B (2 mmol/L ammonium acetate, 0.1% formic acid in 95% acetonitrile, v/v/v) were used for gradient elution. A linear calibration curve was obtained over the range of 0.05–50 mg/L, and the correlation coefficients were better than 0.999. The limit of quantitation was 0.05 mg/L for both analytes. The intra‐ and interday accuracy and precision at three concentration levels ranged between 1.6 and 13.3%, and recoveries were achieved with a range between 92.2 and 114.2%. This method was developed and validated for the therapeutic monitoring of acyclovir in patients.

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Quantification of acyclovir in dermal interstitial fluid and human serum by ultra‐high‐performance liquid–high‐resolution tandem mass spectrometry for topical bioequivalence evaluation

Cited by 11 publications

References 23 publications

Cytokine and Chemokine Recovery Is Increased by Colloid Perfusates during Dermal Microdialysis

Cytokine and Chemokine Recovery Is Increased by Colloid Perfusates during Dermal Microdialysis

Critical Review of Synthesis, Toxicology and Detection of Acyclovir

Determination of acyclovir and its metabolite 9‐carboxymethoxymethylguanide in human serum by ultra‐high‐performance liquid chromatography‐tandem mass spectrometry

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