Adsorptive Cathodic Stripping Voltammetry for Quantification of Alprazolam

A simple and highly sensitive electrochemical sensor was developed for adsorptive cathodic stripping voltammetry of alprazolam. Based on an electrochemically pretreated glassy carbon electrode, the sensor demonstrated good adsorption and electrochemical reduction of alprazolam. The morphology of the glassy carbon electrode and the electrochemically pretreated glassy carbon electrode were characterized by scanning electron microscopy/energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, cyclic voltammetry, and electrochemical impedance spectroscopy. The electrochemical behaviors of alprazolam were determined by cyclic voltammetry, and the analytical measurements were studied by adsorptive cathodic stripping voltammetry. Optimized operational conditions included the concentration and deposition time of sulfuric acid in the electrochemical pretreatment, preconcentration potential, and preconcentration time. Under optimal conditions, the developed alprazolam sensor displayed a quantification limit of 0.1 mg L⁻¹, a detection limit of 0.03 mg L⁻¹, a sensitivity of 67 µA mg⁻¹ L cm⁻² and two linear ranges: 0.1 to 4 and 4 to 20 mg L⁻¹. Sensor selectivity was excellent, and repeatability (%RSD < 4.24%) and recovery (82.0 ± 0.2 to 109.0 ± 0.3%) were good. The results of determining alprazolam in beverages with the developed system were in good agreement with results from the gas chromatography–mass spectrometric method.     

Effect of alprazolam on rat serum metabolic profiles

We developed a serum metabolomic method by gas chromatography–mass spectrometry (GC–MS) to evaluate the effect of alprazolam in rats. The GC–MS with HP‐5MS (0.25 μm × 30 m × 0.25 mm) mass was conducted in electron impact ionization (EI) mode with electron energy of 70 eV, and full‐scan mode with m /z 50–550. The rats were randomly divided to four groups, three alprazolam‐treated groups and a control group. The alprazolam‐treated rats were given 5, 10 or 20 mg/kg (low, medium, high) of alprazolam by intragastric administration each day for 14 days. The serum samples were corrected on the seventh and fourteenth days for metabolomic study. The blood was collected for biochemical tests. Then liver and brain were rapidly isolated and immersed for pathological study. Compared with the control group, on the seventh and fourteen days, the levels of d ‐glucose, 9,12‐octadecadienoic acid, butanoic acid, l ‐proline, d ‐mannose and malic acid had changed, indicating that alprazolam induced energy metabolism, fatty acid metabolism and amino acid metabolism perturbations in rats. There was no significant difference for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea and uric acid between controls and alprazolam groups. According to the pathological results, alprazolam is not hepatotoxic. Metabolomics could distinguish different alprazolam doses in rats.     

A New Method of Separation of Four Benzodiazepines by RP-CEC

A new method to separate diazepam, nitrazepam, estazolam, alprazolam was established on both C18 and C8 CEC columns. The influence of separation voltage, Tris concentration, column temperature and the percentage of acetonitrile on the resolution and retention behavior of four benzodiazepines was investigated. The results showed that the percentage of acetonitrile had the largest effect on the resolution and retention behavior of the four benzodiazepines. Other separation conditions had also effects on the resolution and retention behavior, but smaller than the concentration of acetonitrile. Optimum separation conditions were obtained to separate four benzodiazepines on C18 and C8 CEC columns.     

催眠镇静药甲基三唑安定的合成

本文以对氯硝基苯为起始原料,经六步反应合成了催眠镇静药８－氯－１－甲基－６－苯基－４Ｈ－［１,２,４］三唑并［４,３－α］［１,４］苯并二氮杂艹卓。各步收率均高于参考文献报道收率。总收率由老工艺的２０．８％提高到现在的３４．６％。所得产品经元素分析,ＵＶ,ＩＲ,１ＨＮＭＲ,ＭＳ等光谱分析,证明结构正确。     

Compritol-Based Alprazolam Solid Lipid Nanoparticles for Sustained Release of Alprazolam: Preparation by Hot Melt Encapsulation

The current study was designed to investigate the feasibility of incorporating the water-insoluble lipophilic drug Alprazolam (Alp) into solid lipid nanoparticles (SLNs) to offer the combined benefits of the quick onset of action along with the sustained release of the drug. Therefore, compritol-based alprazolam-loaded SLNs (Alp-SLNs) would provide early relief from anxiety and sleep disturbances and long-lasting control of symptoms in patients with depression, thereby enhancing patient compliance. The optimized Alp-SLNs analyzed by DLS and SEM showed consistent particle size of 92.9 nm with PI values and standard deviation of the measurements calculated at <0.3 and negative surface charge. These characteristic values demonstrate the desired level of homogeneity and good physical stability of Alp-SLNs. The SLNs had a good entrapment efficiency (89.4%) and high drug-loading capacity (77.9%). SEM analysis revealed the smooth spherical morphology of the SLNs. The physical condition of alprazolam and absence of interaction among formulation components in Alp-SLNs was confirmed by FTIR and DSC analyses. XRD analysis demonstrated the molecular dispersion of crystalline alprazolam in Alp-SLNs. The in vitro release study implied that the release of Alp from the optimized Alp-SLN formulation was sustained as compared to the Alp drug solution because Alp-SLNs exhibited sustained release of alprazolam over 24 h. Alp-SLNs are a promising candidate to achieve sustained release of the short-acting drug Alp, thereby reducing its dosing frequency and enhancing patient compliance.     

Stability studies of alprazolam tablets: effects of chemical interactions with some excipients in pharmaceutical solid preparations

An HPLC method was developed to determine the stability of alprazolam (AL) as a pure drug and in monodrug pharmaceutical tablets. The main degradation product of AL tablets was isolated and fully characterized as triazolaminoquinoleine (TAQ). For a quantitative evaluation of the excipient effects in the pharmaceutical formulations, a 2^k fractionated factorial design was applied in the preparation of the different samples. The kinetic of degradation of AL in each formulation was followed by UV spectrophotometry. It was found that excipients like CMC and magnesium stearate favour degradation, while the rate of the reaction is decreased when lactose and starch were used as excipients. A mechanism for the interactions of AL with some excipients is postulated that explains the observed results. Copyright © 2009 John Wiley & Sons, Ltd.     

Estimation of Alprazolam and Sertraline in Pure Powder and Tablet Formulations by High-Performance Liquid Chromatography and High-Performance Thin-Layer Chromatography

Abstract

This article describes validated high-performance liquid chromatographic (HPLC) and high-performance thin-layer chromatographic (HPTLC) methods for simultaneous estimation of alprazolam (ALZ) and sertraline (SER) in pure powder and tablet formulation. The HPLC separation was achieved on a Nucleosil C18 column (150 mm long, 4.6 mm i.d., and 5-µm particle size) using acetonitrile and phosphate buffer (50 + 50 v/v), pH 5.5, as the mobile phase at a flow rate of 1.0 mL/min at ambient temperature. The HPTLC separation was achieved on an aluminum-backed layer of silica gel 60 F₂₅₄ using acetone/toluene/ammonia (6.0:3.0:1.0, v/v/v) as the mobile phase. Quantification with the HPLC method was achieved with ultraviolet (UV) detection at 230 nm over the concentration range 3–18 µg/mL for both drugs with mean recovery of 101.86 ± 0.21 and 100.57 ± 0.31% for ALZ and SER, respectively. Quantification in HPTLC was achieved with UV detection at 230 nm over the concentration range of 400–1400 ng/spot for both drugs with mean recoveries of 101.32 ± 0.15 and 100.38 ± 0.51% for ALZ and SER, respectively. These methods are rapid, simple, precise, sensitive, and are applicable for the simultaneous determination of ALZ and SER in pure powder and formulations.     

Biodegradation of Alprazolam in Pharmaceutical Wastewater Using Mesoporous Nanoparticles-Adhered Pseudomonas stutzeri

The release of pharmaceutical wastewaters in the environment is of great concern due to the presence of persistent organic pollutants with toxic effects on environment and human health. Treatment of these wastewaters with microorganisms has gained increasing attention, as they can efficiently biodegrade and remove contaminants from the aqueous environments. In this respect, bacterial immobilization with inorganic nanoparticles provides a number of advantages, in terms of ease of processing, increased concentration of the pollutant in proximity of the cell surface, and long-term reusability. In the present study, MCM-41 mesoporous silica nanoparticles (MSN) were immobilized on a selected bacterial strain to remove alprazolam, a persistent pharmaceutical compound, from contaminated water. First, biodegrading microorganisms were collected from pharmaceutical wastewater, and Pseudomonas stutzeri was isolated as a bacterial strain showing high ability to tolerate and consume alprazolam as the only source for carbon and energy. Then, the ability of MSN-adhered Pseudomonas stutzeri bacteria was assessed to biodegrade alprazolam using quantitative HPLC analysis. The results indicated that after 20 days in optimum conditions, MSN-adhered bacterial cells achieved 96% biodegradation efficiency in comparison to the 87% biodegradation ability of Pseudomonas stutzeri freely suspended cells. Kinetic study showed that the degradation process obeys a first order reaction. In addition, the kinetic constants for the MSN-adhered bacteria were higher than those of the bacteria alone.     

气相色谱/质谱法测定猪肉中4种苯二氮(艹卓)类镇静剂残留

建立了同时测定猪肉中4种苯二氮类药物(地西泮、艾司唑仑、阿普唑仑、三唑仑)残留量的固相萃取气相色谱质谱方法。用乙腈提取药物,C18固相萃取柱净化,GC/MS分析。运用HP5毛细管柱(30m×0.25mm×0.25μm)进行分离,电子轰击电离源(EI)质谱选择离子模式(SIM)检测(地西泮m/z241、256、257、284;艾司唑仑m/z205、239、259、294;阿普唑仑m/z204、273、279、308;三唑仑m/z238、313、315、342),外标法定量(定量离子m/z分别为256、259、270和313)。4种苯二氮类药物的标准曲线线性回归系数均在0.99以上,地西泮线性范围超过5～100μg/L;回收率为60%～70%;相对标准偏差7.6%～12.9%,最低检出限为2μg/kg。艾司唑仑、阿普唑仑、三唑仑3种药物的线性范围超过50～1000μg/L;回收率为60%～115%;相对标准偏差3.8%～19.7%,检出限为10μg/kg。     

Detection and Quantification of Alprazolam Added to Long Drinks by Near Infrared Spectroscopy and Chemometrics

In the present work, a fast, relatively cheap, and green analytical strategy to identify and quantify the fraudulent (or voluntary) addition of a drug (alprazolam, the API of Xanax^®) to an alcoholic drink of large consumption, namely gin and tonic, was developed using coupling near-infrared spectroscopy (NIR) and chemometrics. The approach used was both qualitative and quantitative as models were built that would allow for highlighting the presence of alprazolam with high accuracy, and to quantify its concentration with, in many cases, an acceptable error. Classification models built using partial least squares discriminant analysis (PLS-DA) allowed for identifying whether a drink was spiked or not with the drug, with a prediction accuracy in the validation phase often higher than 90%. On the other hand, calibration models established through the use of partial least squares (PLS) regression allowed for quantifying the drug added with errors of the order of 2–5 mg/L.