Stability‐indicating HPLC method for simultaneous quantification of 14 impurities in excedrin tablet formulations and identification of new impurity by LC–MS in accelerated stability studies

We developed novel stability‐indicating HPLC method for simultaneous estimation of 14 impurities in excedrin tablet, a formulation with a combination of acetaminophen, aspirin, and caffeine. In addition, a new impurity that was generated through degradation of aspirin at high temperatures during the accelerated stability conditions was positively identified and confirmed, using liquid chromatography–mass spectrometry technique. The HPLC method was optimized using the Inertsustain C₁₈, 250 × 4.6 mm, 5.0 μm column, employing simple gradient method. Forced degradation studies were performed under acidic, basic, oxidative and thermal conditions to prove the scope and stability‐indicating the nature of the method. The optimized method was validated as per the International Conference on Harmonization guidelines. The HPLC method showed linearity from LOQ concentration to 21 μg mL^?1. Precision and intermediate precision values were <5% RSD. The validated HPLC method is currently applied for the routine testing of excedrin tablet formulations in quality control laboratories.     

Simultaneous Determination of Acetaminophen and Phenobarbital in Suppositories by Partial Least-Squares Spectrophotometric Calibration

Abstract

The use of partial least-squares spectrophotometric calibration for the simultaneous determination of suppositories in a multicomponent formulation is presented. This method is applied to the deternination of acetaminophen and phenobarbital in suppository preparations. The results show that these components in a molar ratio of about 61:1 in suppositories have been determined simultaneously with high precision.     

Electrochemical Simultaneous Sensing of Melatonin,Dopamine and Acetaminophen at Platinum Doped and Decorated Alpha Iron Oxide

Simultaneous sensing of dopamine (DA), acetaminophen (AP) and melatonin (MEL) was made by electrochemical method as the drugs melatonin and acetaminophen interact with dopamine in brain to induce neuro disorders. The glassy carbon electrode surface was modified with un‐doped α‐ Fe₂O₃, platinum doped Fe₂O₃ (dPtFe₂O₃), Pt decorated Fe₂O₃ (sPtFe₂O₃) and doped and decorated Fe₂O₃ (sdPtFe₂O₃) nano particles that are synthesized by co‐precipitation method in presence of polyethylene glycol for the first time. These particles were characterized using Ultra‐Violet Visible (UV‐Vis), scanning electron microscopy (SEM), X‐ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR), thermo gravimetric analysis (TGA) and electrochemical techniques. The sdPtFe₂O₃ showed the highest catalytic activity than the dPtFe₂O₃, sPtFe₂O₃ and un‐doped α‐ Fe₂O₃ with well separated voltammetric peaks for DA and AP in presence of MEL. This is attributed to higher surface hydration effects of the sdPtFe₂O₃, dPtFe₂O₃ and sPtFe₂O₃ than the un‐doped Fe₂O₃ which plays a vital role in enhancing the melatonin sensing in presence of dopamine and acetaminophen. Linear ranges and lowest detection limits for all three analytes were increased by 10 times for the sdPtFe₂O₃ compared to other Fe₂O₃ modified electrodes. The sensor is validated using commercially available pharmaceutical drugs used in therapeutics.     

鲁米诺-过氧化氢-纳米银化学发光体系测定药物中的对乙酰氨基酚

碱性条件下,对乙酰氨基酚对鲁米诺-过氧化氢-纳米银化学发光体系有较强的抑制作用,基于此,结合流动注射技术,建立了测定对乙酰氨基酚的新方法。 研究了影响化学发光强度的各种因素,并初步探讨了可能的发光机理。 在最佳实验条件下,对乙酰氨基酚浓度在2.0×10-8～1.0×10-4 mol/L范围内与相对发光强度呈线性关系,检出限(3σ)为4.0×10-9 mol/L。 对1.0×10-7 mol/L的对乙酰氨基酚平行测定9次,相对标准偏差为2.6%。 该法用于片剂中扑热息痛含量的测定,结果令人满意。     

Practical Synthesis of N‐Alkyl‐N‐alkyloxycarbonylaminomethyl Prodrug Derivatives of Acetaminophen,Theophylline, and 6‐Mercaptopurine

We report a novel synthesis of N‐alkyl‐N‐alkyloxycarbonylaminomethyl (NANAOCAM) prodrugs of acetaminophen, theophylline, and 6‐mercaptopurine by alkylation of the corresponding drug molecule with N‐alkyl‐N‐alkyloxycarbonylaminomethyl chlorides in good yield. Most of the alkylating agents were efficiently synthesized by chloromethylation of N‐alkyl carbamic acid alkyl esters, which in turn were made from alkyl amines and alkyl chloroformates. In cases where the alkyl chloroformates were not available, synthesis of N‐alkyl carbamic acid alkyl esters was accomplished by converting an alcohol to a chloroformate or to an activated acylating agent such as acyl imidazoles or p‐nitrophenylcarbonate esters, followed by their reaction with alkyl amines.     

Electrochemistry of electropolymerized tetra (p-aminophenyl)porphyrin nickel film electrode and catalytic oxidation of acetaminophen

A polymer film of tetra(p-aminophenyl) porphyrin nickel was obtained at a glassy carbon electrode by a cyclic voltammetric method. Cyclic voltammograms of the film electrode exhibited two stable redox waves with anodic peak potential at 0.43V and cathodic peak potential at 0.30 V in 0.5M NaOH aqueous solution. The electrocatalytic characteristics of the film electrode were studied by cyclic voltammetry, a. c. impedance analysis and other methods. The oxidation peak current increased linearly with the addition of acetaminophen to the aqueous NaOH medium in the range 1 × 10^–6–2 × 10^–4 M acetaminophen. The performance of the electrode was verified by the determination of acetaminophen in a paracetamol preparation.     

Miniaturized CE System Based on Amperometric Detection and Horizontal Sampling

A novel miniaturized capillary electrophoresis (CE)-amperometric detection system has been fabricated by integrating a self-positioning electrode system and a 10-cm piece of fused silica capillary on a Plexiglas base plate. The self-positioning electrode system was composed of a disc working electrode positioned opposite the outlet of the capillary, with an Ag/AgCl reference electrode, a platinum auxiliary electrode, and a platinum grounding electrode accommodated in a rectangular detection cell on the plate. The platinum wire, close to the inlet of capillary, served as a contact to the high-voltage power supply. Alternate placement of the capillary inlet in vials containing sample or buffer solutions permits volume-defined electrokinetic sample introduction in a horizontal arrangement. Performance of this unique system was demonstrated by separating sugars, amino acids, and two phenols used in the pharmaceutical industry. The factors influencing the analytical performance of the new microsystem for the separation of p-aminophenol and acetaminophen have been characterized and optimized. The two analytes could be separated on baseline within 160s in 50mM acetate buffer (pH 5.0). Responses for p-aminophenol and acetaminophen were linear over the range of 10 to 1000µM with detection limits (S/N=3) of 2.1 and 2.9µM.     

Adiabatic calorimetry and thermal analysis on acetaminophen

Molar heat capacities of acetaminophen were precisely measured with a small sample precision automated adiabatic calorimeter over the temperature range from 80 to 330 K. A solid-solid transition at 149.96 K was found from the C_p,m-T curve. The polynomial functions of C_p,.m(J K^-1 mol^-1) vs. T were established on the heat capacity measurements by means of the least square fitting method. Thermal decomposition processes of acetaminophen have been studied by thermogravimetry. And the thermal decomposition kinetics parameters, such as activation energy E, pre-exponential factor A and reaction order n, were calculated by TG-DTG techniques with the Freeman-Carroll method, Kissinger method and Ozawa method. Accordingly the thermal decomposition kinetics equation of acetaminophen is expressed as: dα/dt=2.67·10⁷e^-89630/RT(1-α)^0.23. The process of fusion has been investigated through DSC. The melting point, molar enthalpy and entropy of fusion are to be (441.89±0.04) K, 26.49±0.44 kJ mol^-1 and 59.80±1.01 J K^-1 mol^-1, respectively.     

毛细管电泳安培检测扑热息痛及其水解物

研究了各种电化学预处理条件下碳纤维电极对扑热息痛及水解物的电化学行为。确定该体系最佳预处理条件为０．２Ｖ电位下阳极化１ｍｉｎ，再于－２．０Ｖ下阴极化１０ｓ。预处理后的碳纤维伏安响应得到明显提高。运用最佳条件并在支持电解中加入添加剂后，扑热息痛及其水解物在毛细管电泳上获得很好的分离和检测。其中扑热息痛的检测下限为２．７８ｐｇ；对氨基酚为１．８４ｐｇ。     

Detection of acetaminophen using cyclic voltammetry on MnFe2O4/polyaniline

A novel sensing material, MnFe₂O₄/polyaniline (PANI), was fabricated by doping PANI to MnFe₂O₄ on a modified glassy carbon electrode (GCE). This sensing material was characterized using X‐ray diffraction (XRD), scanning electron microscopy (SEM), and high‐resolution transmission electron microscopy (HR‐TEM). Using a cyclic voltammetry electrochemical‐sensing method, we tested MnFe₂O₄/PANI, and an acetaminophen concentration of 0.0625–5 mM was recorded. Furthermore, the sensor responses were 2.05–22.44. The detection limit was 2.23 × 10^?7 M. Strong selectivity was observed for MnFe₂O₄/PANI, which is a possible sensing mechanism.