A new extraction method was developed for isolation of the antihistaminic drugs (histamine H2 receptor antagonists) famotidine (FMT) and nizatidine (NZT) from aqueous samples. A low solvent consumption method using dispersive liquid-liquid microextraction (DLLME) was applied for this purpose. The parameters of the isolation, namely, volume of extraction and disperser solvents, pH of sample and shaking time were optimized. The influence of foreign substances on the extraction process was also studied. After separation of FMT and NZT using DLLME, the analytes in organic extracts were determinated by high-performance liquid chromatography combined with UV spectrophotometry and liquid chromatography connected with tandem mass spectrometry (LC-MS-MS). The use of DLLME for selective isolation of analytes enables their preconcentration. Enrichment factors 23 and 61 were obtained for FMT and NZT, respectively. These procedures enable detection of the analytes in real samples at levels 0.24 μg mL-1 (limits of detection (LOD) of FMT: 7.2·10-7 mol L-1 and LOD of NZT: 7.3·10-7 mol L-1). The method was applied for the determination of the studied antihistaminic drugs in river water and wastewater samples. The use of LC-MS-MS in conjunction with DLLME enabled detection of FMT in Netta river at a concentration level of 0.46 ± 0.04 ng mL-1.

Colon microbiota-based drug metabolism has received little attention thus far in the process of drug development, whereas the role of gut microbiota in clinical safety and efficacy of drugs has become more clear. Many of these studies have been performed using animal studies, but the translational value of these data with respect to drug pharmacokinetics, efficacy, and safety is largely unknown. To investigate human colon microbiota-mediated drug metabolism, we applied a recently developed ex vivo fermentation screening platform, in which human colonic microbiota conditions are simulated. A set of 12 drugs (omeprazole, simvastatin, metronidazole, risperidone, sulfinpyrazone, sulindac, levodopa, dapsone, nizatidine, sulfasalazine, zonisamide, and acetaminophen) was incubated with human colon microbiota under strictly anaerobic conditions, and samples were analyzed using high-performance liquid chromatograph-UV-high-resolution mass spectrometry analysis. The human microbiota in the fermentation assay consisted of bacterial genera regularly encountered in human colon and fecal samples and could be reproducibly cultured in independent experiments over time. In addition, fully anaerobic culture conditions could be maintained for 24 hours of incubation. Five out of the 12 included drugs (sulfasalazine, sulfinpyrazone, sulindac, nizatidine, and risperidone) showed microbiota-based biotransformation after 24 hours of incubation in the ex vivo fermentation assay. We demonstrated that drug metabolites formed by microbial metabolism can be detected in a qualitative manner and that the data are in accordance with those reported earlier for in vivo metabolism. In conclusion, we present a research tool to investigate human colon microbiota-based drug metabolism that may be applied to enable translatability of microbiota-based drug metabolism.

In the 1980s-1990s numerous studies were performed on H2-receptor antagonist inhibition of ethanol first-pass metabolism. Blood alcohol concentrations warranting possible driving under the influence citations in the United States have subsequently dropped from ≥100 mg/dL to 50 mg/dL (Utah in 2019) (30 mg/dL or zero tolerance in some parts of the world). A reexamination of these studies seemed important. Areas covered: Papers were compiled that addressed the effect of cimetidine, ranitidine, famotidine, and nizatidine on ethanol metabolism first from a PubMed search and then from citations within these papers. Studies were tabulated for fasting versus fed, ethanol and H2-receptor antagonist dose and a summary of pharmacokinetic changes. Expert opinion: At doses of 0.15-0.30 mg/kg in the postprandial state (primarily after breakfast), the H2-receptor antagonists: cimetidine, ranitidine, famotidine, and nizatidine have all been found to increase the first-pass metabolism of ethanol. With cimetidine, there were sufficient studies to suggest it might be inhibitory outside these restricted states. While the role of inhibition of alcohol dehydrogenase has not been clearly defined, there is circumstantial evidence to support this mechanism. Further studies are required to elucidate the ability of H2-receptor antagonists to inhibit first-pass metabolism of ethanol.

Because of the low levels of nizatidine in breastmilk, amounts ingested by the infant are small and would not be expected to cause any adverse effects in breastfed infants. No special precautions are required. Histamine H2-antagonists with more extensive use might be preferred in newborns.

Nizatidine has been labeled using [125 I] with chloramine-T as oxidizing agent. Factors such as the amount of oxidizing agent, amount of substrate, pH, reaction temperature, and reaction time have been systematically studied to optimize the iodination. Biodistribution studies indicate the suitability of radioiodinated nizatidine as a novel tracer to image stomach ulcer. Radioiodinated nizatidine may be considered a highly selective radiotracer for peptic ulcer imaging.

A comparative force degradation high performance thin layer chromatography (HPTLC) method was developed and validated for some H2-receptor antagonists. The studied H2-receptor antagonists were ranitidine (RAN), nizatidine (NIZ) and famotidine (FAM). The degradation behaviors of the studied H2-receptor antagonists were studied under different stress conditions (hydrolytic, thermal and oxidative) conditions as well as storage conditions according to International Conference on Harmonization (ICH) recommendations. A stability-indicating HPTLC method was optimized in order to separate the analyte from the degradation products formed under various stress conditions. Full separation of the drugs from their degradation products was successfully achieved on an HPTLC precoated silica gel plates. Densitometric measurements were carried out using a Camag TLC Scanner III in the absorbance mode at 320 nm for RAN and NIZ, and 280 nm for FAM. The limits of detection and limits of quantitation range were 5.47-9.37 and 16.30-31.26 ng/band, respectively, for all investigated drugs. The validation studies were performed according to ICH requirements. The developed method was simple, rapid and reliable hence it could be applied for routine quality control analysis of the investigated H2-receptor antagonists in dosage forms. The kinetic behavior, degradation rate constants and half-lives of the degradation of the investigated drugs were studied and compared at different stress conditions. The present study provides, for the first time, a new vision to compare the degradation kinetics of H2-receptor antagonists at the same degradation procedures.

This study investigated the degradation kinetics and halonitromethanes formation potential (HNMsFP) of two nitro-based pharmaceuticals (i.e., ranitidine (RNTD) and nizatidine (NZTD)) during ultraviolet (UV) photolysis. It was found that the degradation kinetics of RNTD and NZTD exhibited pH-dependent trends, in accordance with their deprotonation equilibria. The neutral species of RNTD and NZTD were more photo-reactive than their corresponding deprotonated species, with their specific fluence-based first-order rate constants varying in the range of 5.64-31.90 m(2) E(-1). Both the RNTD and NZTD were prone precursors of HNMs (with molar yields of 5.6± 0.3% and 4.7± 0.4%, respectively at pH 7.0). Acidic and neutral circumstances facilitated the HNMs formation. The UV photolysis of RNTD and NZTD could reduce their HNMsFP simultaneously. Positive linear relationships between residual RNTD or NZTD concentration and HNMsFP were observed and the denitration during the UV photolysis accounted for the HNMsFP reduction. With the mandatory UV disinfection fluences in China (i.e. 20-80 mJ cm(-2)), the effective abatement of RNTD and NZTD and their HNMsFP could not be fully achieved, highlighting the necessity of increasing UV fluence or developing UV-based advanced oxidation process in future.

The dielectric properties of two pharmaceuticals nizatidine and perphenazine were investigated in the supercooled liquid and glassy states by broadband dielectric spectroscopy. Two relaxation processes were observed in both the pharmaceuticals. The relaxation process observed above the glass transition temperature is the structural alpha relaxation and below the glass transition temperature is the gamma relaxation of intramolecular origin. The Johari-Goldstein beta relaxation coming from the motion of the entire molecule is found to be hidden under the structural relaxation peak in both the pharmaceuticals.