Hydrochloride Research Articles

Status and Rationality of Opioid Use in Lung Cancer Patients: A Single Center Retrospective Study

背景与目的癌痛严重影响患者体力活动、心理状态以及生活质量，甚至缩短患者生存时间，合理规范应用阿片类药物可有效控制癌痛。肺癌患者癌痛发病率高，需分析肺癌患者阿片类药物应用现状，以评估肺癌患者阿片类药物应用的合理性。方法回顾性分析2018年6月-2019年6月北京协和医院呼吸与危重症医学科肺癌住院患者的临床资料，分析305例应用阿片类药物的肺癌癌痛患者的临床信息和用药信息。结果应用阿片类药物的肺癌患者影响因素分析中，年龄与阿片药物应用种类为主要影响因素。男性比例高于女性，且男性患者应用阿片药物种类多、年龄多集中在60岁-69岁之间。我院肺癌患者应用阿片类药物品种和结构符合要求，用药频率最高的为羟考酮缓释片，限定日费用（defined daily cost, DDC）排名第一位同时序号比为1，同步性好。吗啡片和吗啡注射液用量低，肺癌患者整体爆发痛（breakthrough cancer pain, BTcP）控制良好。阿片类药物整体应用合理（93.4%），不合理项目主要为爆发痛处置和用药频率不合理以及超剂量问题。结论应用阿片类药物的肺癌癌痛患者多为男性，老年男性癌痛更难于控制，需要加强关注。我院肺癌患者阿片类药物整体应用合理，但仍需关注BTcP处置、阿片类药物用药剂量和特殊人群用药等问题。

A novel amphipathic low-melting complex salt: An efficient homogeneous catalyst for synthesis of pyran-annulated heterocyclic scaffolds and pyrido[2,3-d]pyrimidines

Abstract The reaction of triethyl(sulfonyl)ammonium chlorosulfonate with 1,1,3,3-tetramethylguanidine (TMG) gave a low-melting complex salt with amphipathic and acidic characters. The salt has a great tendency towards solvation of organic substrates upon slight heating, so it was employed as a homogeneous acidic and functional ionic liquid catalyst in the expedient synthesis of benzo[b]pyrans, pyrano[4,3-b]pyrans, pyrano[3,2-c]quinolones, and pyrido[2,3-d]pyrimidines. The catalytic activity of the complex salt is much better than the simple salts composing it. Spectroscopic studies and chemical analysis of the salt revealed that its empirical formula is in agreement with neutralization of TMG by two H2SO4 molecules. The HSO4− anions of the salt seem to form extensive H-bonding with the constituting ammonium cations and Cl−, resulting in melting point depression of the complex salt due to the melting points of pure triethylamine and TMG hydrochloride salts. Another significant feature of this solid salt is that it can preserve its composition even after several times of separation from aqueous extracts and can be handled easily without danger.

Potentiometric CheqSol and standardized shake-flask solubility methods are complimentary tools in physicochemical profiling

The solubility of three drugs (glimepiride, pioglitazone, sibutramine) with different acid/base properties and expected supersaturation behavior was examined in detail using the shake-flask (SF) and potentiometric (CheqSol) methods. Both uncharged (free) species and hydrochloride salts were used as starting materials. On the one hand, the SF method provided information about the thermodynamic solubility at any pH value, including the counterion-dependent solubility of ionic species. Additionally, this method easily allowed the identification of the solid phase in equilibrated solutions by powder X-ray diffraction, and the detection and quantification of aggregation and complexation reactions. On the other hand, CheqSol method permitted the measurement of the equilibrium solubility of neutral species, the observation of changes in solid forms, and the extent and duration of supersaturation (kinetic solubility) for “chaser” compounds. The combined information from both methods gave an accurate picture of the solubility behavior of the studied drugs.

Preparation of hierarchical SAPO-18 via alkaline/acid etching

Abstract Hierarchical SAPO-18 molecular sieve was successfully post-synthesized in the alkaline tetraethyl ammonium hydroxide (TEAOH) solution and hydrochloride (HCl) acid solution. In the TEAOH solution, preferential dissolution occurs surrounding the defect sites in a controlled manner, leading to hierarchical SAPO-18 with well-preserved chemical compositions and crystallinities. In acidic solution, the dissolution is revealed to be sensitive to both the defects and the chemical compositions (selective dissolution of the Si-O-Al domains), which cooperatively contribute to the generation of meso-/macropores in the crystals. The crystallization of SAPO-18 precursor is thus inferred to proceed via an oriented nanoparticle attachment mechanism in the early stage. The twinning and intergrowth of nanoparticles occur in an ordered way, leading to the oriented arrangement of the crystallite boundaries. The defects located at the intergrowth interface are prone to acid/alkaline attacks, and play crucial role in the development of hierarchical pore systems. The hierarchical SAPO-18 sample exhibits excellent catalytic reaction performance in the liquid phase benzylation reaction of benzene and benzyl alcohol.

Rapid Method for the Determination of Thiamine and Pantothenic Acid in Infant Formula and Milk-Based Nutritional Products by Liquid Chromatography‒Tandem Mass Spectrometry.

Thiamine and pantothenic acid play a critical role in numerous metabolic reactions and are typically supplemented in infant and adult nutritional formulas as thiamine chloride hydrochloride and calcium pantothenate salts. A rapid compliance method for the analysis of thiamine and pantothenic acid applicable to infant formula and milk-based nutritional products is described. Proteins are removed by centrifugal ultrafiltration, followed by analysis by reversed-phase liquid chromatography‒tandem mass spectrometry (LC-MS/MS), with quantitation accomplished by internal standard technique. The method was shown to be accurate, with acceptable recovery (thiamine, 99.3-101.1%; pantothenic acid, 99.2-108.6%). A certified reference material (NIST 1849a), showed no statistical bias (α = 0.05) for thiamine (P = 0.64); although a statistically significant bias (P < 0.01) for pantothenic acid was found, the nominal bias was only 4.7% (mean = 7.1 mg/hg; certified value = 6.8 mg/hg). A comparison of results by LC-MS/MS and current methods showed negligible bias (mean bias: thiamine, 0.01 mg/hg; pantothenic acid, 0.17 mg/hg) and no statistical significance (α = 0.05; thiamine, P = 0.399; pantothenic acid, P = 0.058). Acceptable precision was demonstrated with a repeatability of 7.2% repeatability relative standard deviation (RSDr) (HorRat: 0.6) and an intermediate precision of 7.0% RSD for thiamine, and a repeatability of 5.7% RSDr (HorRat: 0.5) and an intermediate precision of 6.1% RSD for pantothenic acid. This rapid method is intended for use in high-throughput laboratories as part of routine product compliance release testing of thiamine and pantothenic acid in manufactured infant and milk-based nutritional products.

Evaluation of interference factors in creatinine measurement by using new guideline CLSI EP7-A3

Objective To investigate the interfering factors in the determination of creatinine(Cr) using the American Clinical Laboratory Standards Association (CLSI) EP7-A3 document. Methods According to the CLSI EP7-A3 document, fresh serum (no hemolysis, lipemia, and jaundice) was used on the day of the experiment and confirmed the interfering substances through the pairing difference experiment and the point-to-point analysis method was used in the dose effect experiment to clarify the difference of interfering substances. Results Triglyceride (16.94 mmol/L), dobutamine hydrochloride (4.01 μmol/L), ascorbic acid (298 μmol/L) did not interfere with the determination of Cr. Free bilirubin (684 μmol/L), conjugated bilirubin (684 μmol/L), calcium hydroxybenzene sulfonate (144 μmol/L) and hemoglobin (10 g/L) were used as the maximum concentrations of interferences for the dose effect test, the results showed that the above interferences had negative interference on the determination of Cr. Conclusion According to EP7-A3, it is valuable to evaluate the interference factors of creatinine determination. Key words: Interference experiment; Creatinine

Drug utilization review of tramadol hydrochloride in a regional hospital in South Africa; findings and implications

ABSTRACT Background Drug utilization reviews (DURs) can be used to promote rational prescribing and ensure compliance with standard treatment guidelines. In recent years, the use of tramadol hydrochloride (HCl) for pain has increased significantly across countries. We sought to determine prescribing patterns and the use of tramadol in a regional hospital in South Africa to provide future guidance in view of increasing concerns with the prescribing of tramadol. Method A prospective, quantitative and descriptive study was conducted over two months. Outpatient and inpatient prescriptions and ward requisitions where tramadol HCl was prescribed or ordered were identified, which included outpatients collecting antiretroviral treatment. Prescriptions were reviewed and evaluated to determine the level of compliance to the Standard Treatment Guidelines and Essential Medicines List (STGs/EML) for South Africa as a measure of rational prescribing. Quantities issued to the inpatient wards and expenditure incurred by the pharmacy departments were assessed to determine overall usage and total costs. Results In total, 415 tramadol HCl prescriptions were collected over a 2-month period. Compliance was 70.1% to the STGs/EML. The outpatient pharmacy department had the highest compliance at 76.4% while the antiretroviral pharmacy compliance was 29.1%. Most prescriptions dispensed at the outpatient pharmacy were from the Surgical Outpatient Department (140; 33.7%) and the Orthopedic Outpatient Department (108; 26.0%). The outpatient pharmacy had the highest tramadol HCl consumption and expenditure at $4,874.13 (R72,054.28), while the inpatient pharmacy’s expenditure was $2,526.63 (R37,351.20), and the antiretroviral pharmacy $590.13 (R8,722.75). The hospital’s tramadol HCl expenditure increased when compared to previous financial years, from $10,576.04 (R156,326.00) in 2014–2015 to $39,584.00 (R585,088.80) in 2016–2017. Conclusion This study highlights the need for the implementation of monitoring and evaluation tools to enhance rational prescribing and use of tramadol HCl. These are being implemented and will be evaluated in future projects.

Simple and sensitive electrochemical determination of higenamine in dietary supplements using a disposable pencil graphite electrode

In this study, a cheap, rapid, simple, and modification-free electroanalytical methodology based on the disposable pencil graphite electrode is described for the quantification of higenamine (isoquinoline-type alkaloid having three phenolic OHs). At first, the electrochemical oxidation of higenamine was investigated in aqueous solutions by cyclic voltammetry. The electrode process is pH-dependent and controlled by a mixture of diffusion and adsorption processes. Higenamine yielded two well-separated oxidation steps in acidic, neutral, and alkaline media by using square-wave voltammetry. By using the first oxidation peak due to its higher sensitivity, there was an excellent correlation between oxidation peak current at + 0.44 V and higenamine concentration (as hydrochloride salt) in the range of 0.05 to 2.0 μg cm−3 (1.63 × 10−7–6.5 × 10−6 mol dm−3), with a detection limit of 0.014 μg cm−3 (4.55 × 10−8 mol dm−3) in Britton–Robinson buffer at pH 4.0. As an example, the developed approach can be used for the quantification of higenamine in the commercial dietary supplement formulations.

Oxycodone hydrochloride sustained release tablets combined with radioactive 125iodine seed implantation in the treatment of lung cancer pain: one case report

Oxycodone hydrochloride sustained release tablets combined with radioactive 125iodine seed implantation in the treatment of lung cancer pain: one case report

Reducing the Sublimation Tendency of Ligustrazine through Salt Formation

Two new salts of ligustrazine (tetramethylpyrazine, TMP) with the sweeteners, saccharine (SAC) and acesulfame (ACS), have been synthesized through the anion exchange reaction. Single crystals of the new forms were prepared, and their structures were determined. The stability of the new salts against heat and humidity was tested and compared to the commercial hydrochloride and phosphate salts. The sublimation kinetics at various temperatures was analyzed using the Arrhenius equation. The results indicated that TMP-ACS exhibits significantly reduced sublimation tendency and hygroscopicity, which make it a more suitable salt for developing a tablet with acceptable shelf stability than the salts currently used in commercial products.

Synthesis of a protected 2-aminocyclobutanone as a modular transition state synthon for medicinal chemistry

The hydrochloride salt of ɑ-aminocyclobutanone protected as its dimethyl acetal 2,2-dimethoxycyclobutan-1-aminium chloride (3) has been prepared as a modular synthon for convenient access to cyclobutanone-containing lead inhibitors of hydrolase enzymes including serine proteases and metalloproteases. Protected ɑ-aminocyclobutanone 3 was converted to representative amide and sulfonamide-functionalized 2-aminocyclobutanone derivatives. Reaction of the amino acetal 3 with phenyl isothiocyanate afforded the bicyclic urea 1-hydroxyl-2,4-diazabicyclo[3.2.0]heptane-3-thione (9) as confirmed by a single crystal X-ray structure.

Characteristics of nalbuphine and its application in pediatric anesthesia

Nalbuphine hydrochloride is an agonist-antagonist opioid that has analgesic and sedative effects, which can be used in perioperative period of pediatric patient. Nalbuphine hydrochloride reverses the adverse effects of μ receptor agonist (e.g. nausea, vomiting, itching) without influencing its analgesic effects. Due to the ceiling effect, nalbuphine does not cause respiratory depression. Nalbuphine has a higher safety factor, which makes it one of the most commonly used analgesic in paediatric patients. The application of nalbuphine is more popular in the country, thus, the indications of using nalbuphine in pediatric anesthesia should be clearly defined. The pharmacological properties of nalbuphine, clinical application of pediatric anesthesia were summarized in this review. Key words: Nalbuphine; Pediatric anesthesia; Analgesia; Sedation; Application

Phosgene in deteriorated chloroform: presumptive cause of production of 3,4-dimethyl-5-phenyl-2-oxazolidones in methamphetamine

The trans- and cis-forms of 3,4-dimethyl-5-phenyl-2-oxazolidone (DPO) are impurities found in methamphetamine, but their production mechanism has been unclear. Here, the authors examined whether DPOs were produced by the reaction of ephedrines (ephedrine and pseudoephedrine) with deteriorated chloroform containing phosgene. Two sources of chloroform were used in this experiment: amylene-stabilized chloroform, which had been stored on a laboratory table after opening the bottle, and ethanol-stabilized chloroform, which had been stored without opening the bottle. Samples 1–4 were prepared and analyzed by gas chromatography/mass spectrometry. Sample 1 was prepared by extracting hydrochloride salts of ephedrines with chloroform under basic conditions. Sample 2 represented a chloroform solution of pseudoephedrine hydrochloride. Sample 3 was a methanol solution of pseudoephedrine hydrochloride, which had been exposed to chloroform prior to dissolution. Sample 4 was prepared by extracting pseudoephedrine hydrochloride, which had been exposed to chloroform prior to the extraction, with ethyl acetate under basic conditions. Phosgene was detected in amylene-stabilized chloroform but not ethanol-stabilized chloroform. The amylene-stabilized chloroform almost completely converted ephedrines to DPOs in samples 1 and 2, and partially converted pseudoephedrine to trans-DPO in samples 3 and 4. In contrast, the ethanol-stabilized chloroform did not give DPOs in any sample. The experimental results indicated that DPOs were produced by the reaction of ephedrines with deteriorated chloroform containing phosgene and that the reaction proceeds regardless of chemical forms, even at room temperature. DPOs are useful markers of contact between ephedrines and deteriorated chloroform.

Effects of nalmefene hydrochloride on TLR4 signaling pathway in rats with lung ischemia-reperfusion injury.

To investigate the effect of nalmefene hydrochloride on TLR4 signaling pathway in rats with lung ischemia-reperfusion injury. Altogether 64 pure inbred male SD rats were divided into groups A, B, C, and D according to the principle of body weight similarity, with 24 rats in each group. Four groups of rats were respectively twisted on the left testis to establish unilateral testicular torsion rats. Group A was the control group, treated with normal saline, group B was the nalmefene hydrochloride high-dose group, treated with 20 μg/kg of nalmefene hydrochloride, group C was the nalmefene hydrochloride low-dose group, treated with 10 μg/kg of nalmefene hydrochloride, and group D was the sham operation group. Lung tissue was collected 60 h later. Western blotting was used to detect the expression levels of HMGB1, TLR4, CD14, and NF-κB protein, qPCR was used to detect the mRNA expression level, and enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of inflammatory factors IL-17, IL-6, and ICAM-1. The expression levels of HMGB1, TLR4, CD14, NF-κB protein, mRNA, IL-17, IL-6, and ICAM-1 in group A were significantly higher than those in groups B, C, and D (p<0.05), while were significantly lower in group D than in groups B and C (p<0.05), and were significantly lower in group B than in group C (p<0.05). Nalmefene hydrochloride can effectively inhibit the signal pathway of TLR4, and can effectively reduce the injury caused by lung ischemia-reperfusion. The large dose is closely related to the good effect, which is worthy of promotion.

Anesthetic efficacy and safety of 2% lidocaine hydrochloride with 1:100,000 adrenaline and 4% articaine hydrochloride with 1:100,000 adrenaline as a single buccal injection in the extraction of maxillary premolars for orthodontic purposes.

BackgroundPalatal injection of local anesthetics is the most painful injection. To obviate the need for palatal injections, local anesthetic agents with diffusibility are being investigated. Hence the present study was designed to analyze the anesthetic efficacy of 2% lidocaine hydrochloride (HCl) with 1:100,000 adrenaline and 4% articaine hydrochloride (HCl) with 1:100,000 adrenaline using single buccal infiltration for the extraction of maxillary premolars.MethodsA prospective, double-blind, crossover, randomized clinical study was performed on 60 consecutive systemically healthy patients with an age range of 15-30 years, requiring extraction of asymptomatic bilateral maxillary premolars for orthodontic purposes. They received 1ml buccal infiltration of 4% articaine HCl with 1:100,000 adrenaline on one side and 2% lidocaine HCl with 1:100,000 adrenaline on the other side. The extraction procedure on either side was scheduled 14 days apart. Parameters assessed were the time of onset of anesthesia, intraoperative discomfort, hemodynamic parameters, and the duration of analgesia. Analysis of the data was done using the Mann-Whitney test, the Wilcoxon test, the Kruskal-Wallis ANOVA test, and the chi-square test. Statistical significance was established at P < 0.05.ResultsArticaine showed a faster time of onset and longer duration of analgesia than lidocaine. However, the difference in the intraoperative discomfort and hemodynamic parameters was statistically insignificant.ConclusionWithin the limitations of the study, it can be concluded that the extraction of maxillary premolars can be performed with a single buccal infiltration of 2% lidocaine HCl with 1:100,000 adrenaline, which is one of the most commonly used local anesthetic agent.

Synthesis, structural characterization, physicochemical properties and transformations of dehydroevodiamine and its hydrochloride salts

Five kinds of dehydroevodiamine (DHED) related crystals were harvested and transformations among evodiamine (EVO), DHED, DHED·HCl·2H2O and rutaecarpine (RUT) were revealed.

Sexual dysfunction in tramadol hydrochloride use disorder male patients: a case-control study.

Evidence suggests that opioids can modulate gonadal function, with consequent decreased release of sex hormones. We attempted to investigate the sexual function of males using tramadol hydrochloride (HCL) and its relationship to levels of free testosterone, luteinizing hormone, and follicle stimulating hormone, and to compare them with heroin use disorder patients and healthy controls. Our sample consisted of 60 opiate use disorder patients (assessed by Structured Clinical Interview for DSM-IV Axis I) (30 heroin and 30 tramadol) and 30 healthy controls. Sexual dysfunction was assessed using the International Index of Erectile Function. Free testosterone, follicle stimulating hormone, and luteinizing hormone levels were measured in morning blood samples using enzyme-linked immunosorbent assay (ELISA). Results showed that there was a decrease of luteinizing hormone and free testosterone levels in opiate use disorder patients compared with healthy controls, with heroin-dependent patients having significantly lower levels than those using tramadol. Opiates' effect on follicle stimulating hormone had mixed results. Opioid-dependent patients (both tramadol HCL and heroin using patients) developed sexual dysfunction more than healthy controls, which was generalized, with erectile dysfunction being the most affected domain. These findings are of ultimate importance, considering the fact that people use opioids to enhance their sexual performance in many countries.

Evaluation of the pharmacokinetics and food effects of a novel formulation tamsulosin 0.4 mg capsule compared with a 0.2 mg capsule in healthy male volunteers.

Tamsulosin, an alpha-1 adrenoreceptor antagonist, has been used as a primary option for medical treatment of benign prostate hyperplasia. An open-label, single-dose, randomized, three-treatment, three-period, three sequence crossover study was conducted to evaluate the pharmacokinetics (PKs) of 0.2 and 0.4 mg tamsulosin hydrochloride (HCl) in the fed versus the fasted state. Subjects were randomly assigned to three sequences and received one of the following treatments at each period: tamsulosin HCl 0.2 or 0.4 mg in the fed state with a high-fat meal, or tamsulosin HCl 0.4 mg in the fasted state. Blood samples for the PK analysis were collected at pre-dose and up to 48 h post-dose. The PK parameters were calculated by a non-compartmental method. The geometric mean ratio (GMR) and its 90% confidence intervals (CIs) of the plasma maximum concentration (Cmax) and area under concentration curve from time zero to last measurable concentration (AUClast) were calculated. Twenty-two subjects completed the study. The systemic exposure of tamsulosin 0.4 mg decreased approximately 9% in the fed state compared to the fasted state, and the time to reach peak concentration was slightly delayed in the fed state. The dose normalized GMR and its 90% CIs of Cmax and AUClast for 0.2 and 0.4 mg tamsulosin in the fed state were within 0.8 and 1.25 range. Systemic exposure of tamsulosin was decreased in the fed condition compared to the fasted condition. Linear PK profiles were observed between 0.2 and 0.4 mg tamsulosin in the fed state.Trial RegistrationClinicalTrials.gov Identifier: NCT02529800

Deep Silicon Barrier Structure as Chemical Sensor for Detection of Hydrochloric Acid Salt Solutions

Deep Silicon Barrier Structure as Chemical Sensor for Detection of Hydrochloric Acid Salt Solutions

Transdermal patches of lidocaine/aspirin ionic liquid drug-loaded gelatin/polyvinyl alcohol composite film prepared by freeze-thawed procedure.

The objectives of this study are to prepare a 5 wt% lidocaine/aspirin ionic liquid drug-loaded gelatin/polyvinyl alcohol composite film using a freeze-thaw procedure and to evaluate their physicochemical characteristics, in vitro drug release, and stability. Lidocaine/aspirin ionic liquid drugs can be prepared by an ion-pair reaction between the hydrochloride salts of lidocaine and the sodium salts of aspirin, which showed a significant change in their thermal properties when compared to those pure drugs. The results showed that a transdermal patch could feasibly be used in pharmaceutical transdermal patches with good physicochemical properties. A chemical interaction between the drug and polymer base was not found. Decomposition of the lidocaine/aspirin ionic liquid drug was found in the patch; however, the properties of the patch were not changed after drug loading. The patch controlled the drug release and showed good stability during the studied period of three months when kept at 4°C more than at ambient temperature and 45°C.