Estimation of diuretic drugs in biological fluids by HPLC

Summary This critical review of different methods proposed for the determination and screening of diuretics is directed mainly, because of its potential application, towards highperformance liquid chromatography.     

Gas-phase behaviour of negative ions produced from thiazidic diuretics under electrospray conditions

A systematic mass spectrometric study of 10 thiazidic diuretics and related compounds was undertaken by mass spectrometry (MS) with electrospray ionization in the negative ion mode. Collisional dissociation 'in-source' (CID-MS) and in a low-pressure collision cell (CID-MS/MS) were compared in both excitation regions. Spectra obtained by CID-MS and by CID-MS/MS were matched. Using the two methods, loss of HCl and consecutive dissociations from 2HCl losses were exhibited from compounds such as methyclothiazide and trichlormethiazide but not from other thiazidic diuretics that contain chlorine substituents in the aromatic moiety. However, deprotonated dichlorphenamide gave rise to loss of HCl by CID-MS and CID-MS/MS. For other diuretics such as hydroflumethiazide and hydrochlorothiazide, the loss of HCN and [HCN + SO(2)] was relevant. Reaction mechanisms were checked by means of deuterium-hydrogen exchange, which showed that deprotonation took place regioselectively on the heterocyclic moiety. The cleavage pathways require molecular isomerization forming ion-dipole complexes prior to decompositions, allowing long-distance proton transfer for neutral elimination. Identifications of the most specific fragmentations presented in this paper were applied to the screening and unambiguous identification of diuretics for horse doping control.     

4-Hydroxy-2-quinolones. 47. Synthesis and Diuretic Activity of (2H-1,2,4-Benzothiadiazine-1,1-dioxide-3-yl)methylamides of 1-R-4-Hydroxy-2-oxoquinoline-3-carboxylic Acids

With the aim of investigating the relationship between chemical structure and biological activity we have synthesized and studied the effect of (2H-1,2,4-benzothiadiazine-1,1-dioxide-3-yl)methylamides of 1-R-4-hydroxy-2-oxoquinoline-3-carboxylic acids on kidney urinary output.     

4-Hydroxy-2-quinolones 150*. Efficient synthesis,structure, and biological activities of 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid alkyl amides

A simple and efficient method for preparing 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid alkyl amides is proposed. The results of a study of the diuretic activity of the compounds synthesized are reported. *For communication 149 see [1]. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1841-1848, December, 2008.     

4-Hydroxy-2-quinolones 142. 4-Methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid anilides as potential diuretics

A large series of 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid anilides has been prepared as potential diuretic agents. The effect of all of the synthesized compounds on the urinary function of the kidney has been investigated. The appearance of a “structure — diuretic activity” relationship is discussed. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 239–245, February, 2008.     

基于一种新型有机聚合物整体柱的毛细管电色谱技术用于利尿剂的分离与检测

采用自制的新型有机聚1-十六碳烯-三羟甲基丙烷三甲基丙烯酸酯［poly(1-hexadecene-co-TMPTMA)］整体柱,建立了一种同时分离检测6种利尿剂(氯噻酮、氢氯噻嗪、美托拉宗、吲哒帕胺、坎利酮和螺内酯)的毛细管电色谱(CEC)新方法,并成功应用于志愿者实际尿样的分析测定。在最佳实验条件下,6种利尿剂包含2种中性物质(坎利酮和螺内酯)和2种同分异构体(美托拉宗和吲哒帕胺)在11.0 min内得到基线分离,柱效分别达到218000、176000、143000、121000、108000、103000 塔板/m。6种利尿剂在1.15～86.0 μg/mL范围内呈良好的线性关系,相关系数R2 ≥0.990 8,检出限(LOD)在0.35～0.65 μg/mL范围内,回收率为81.9%~105%,相对标准偏差(RSD)小于4.7%。结果表明,实验所建立的基于poly(1-hexadecene-co-TMPTMA)整体柱的CEC方法,具有良好的重复性和稳定性,能够实现对多种利尿剂的同时分离检测。该方法已成功应用于来自志愿者实际尿样的分析,该方法可以用于利尿剂类药物的初筛。     

气相色谱-质谱联用技术用于利尿剂的快速初筛和确证

利用微波辅助衍生及宏程序技术,对反兴奋剂条例的禁用列表中的一系列利尿剂药物进行了研究。建立了同时分析尿样中9种利尿剂的气相色谱-质谱联用(GC/MS)测定以及抽检尿样的初筛、确证的新方法。在GC-MS的选择离子监测(SIM)模式下,所建立定量方法的检出限为0.3~6.6μg/L;尿样中的提取回收率为37.6%~96.8%;RSD小于9.7%。由于采用了微波衍生样品前处理技术和宏程序数据处理方法,显著提高了分析效率,不但检测灵敏度完全能满足国际奥委会的要求,而且检测时间缩短3 h以上。方法成功地应用于口服吲达帕胺后尿样的检测,探讨了人尿中吲达帕胺代谢情况,有效进行兴奋剂监控提供了依据。     

Interfacing on-line solid phase extraction with monolithic column multisyringe chromatography and chemiluminescence detection: An effective tool for fast, sensitive and selective determination of thiazide diuretics

A new, multisyringe flow injection set-up has been developed for the completely automated determination of trace thiazide compounds with diuretic action in different types of samples. The proposed instrumental set-up exploits for the first time, a low pressure on-line solid phase extraction-liquid chromatography-chemiluminescence detection method. This novel combination of sample treatments in flow systems expands the current applicability of low pressure liquid chromatography due to the isolation/preconcentration of the target compounds, besides high selectivity and sensitivity.For the determination of three thiazide compounds named hydroflumethiazide, furosemide and bendroflumethiazide, the proposed set-up provided with the preconcentration of only 1 mL of sample, limits of detection of 3, 60 and 40 μg L⁻¹, respectively. Furthermore wide linear dynamic ranges of 6-4000, 140-20,000 and 90-40,000 μg L⁻¹, respectively, were obtained. Besides of this, a high injection throughput of 12 h⁻¹ was also achieved. As in sports, thiazide diuretics are prohibited substances, the proposed method has been applied to their determination in urine samples. Furthermore the potential of the proposed method as a fast-screening approach for emerging contaminants in waters has been also tested by applying it to well water and leachates from a solid waste landfill.     

4-Hydroxy-2-quinolones 138. Synthesis and study of structure-biological activity relationships in a series of 1-hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-<Emphasis Type="Italic">ij</Emphasis>]quinoline-2-carboxylic acid anilides

Two methods are discussed and the synthesis of a series of 1-hydroxy-3-oxo-5,6-dihydro-3H-pyrrolo[3,2,1-ij]quinoline-2-carboxylic acid anilides has been carried out. The antitubercular activity and the effect on the urinary function of the kidney have been studied for the compounds prepared. A structure-biological activity relationship is discussed. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1808–1819, December, 2007.     

Development of solid-phase extraction method and its application for determination of hydrochlorothiazide in human plasma using HPLC

A high-performance liquid chromatographic method was developed, validated and applied for the determination of hydrochlorothiazide in human plasma. The effects of mobile phase composition, buffer concentration, mobile phase pH and concentration of organic modifiers on retention of hydrochlorothiazide and internal standard were investigated. The method involves solid-phase extraction on RP-select B cartridges followed by isocratic reversed-phase chromatography on a Hibar Lichrospher 100 RP-8 column with UV detection at 230 nm. The recovery, selectivity, linearity, precision and accuracy of the method were evaluated from spiked human plasma samples. Limit of quantification was 10 ng mL(-1). The method has been implemented to monitor hydrochlorothiazide levels in patient samples.