Review: The physiology of saliva and transfer of drugs into saliva

Although saliva or oral fluid “lacks the drama of blood, the sincerity of sweat and the emotional appeal of tears”, quoting Mandel in 1990 [I.D. Mandel, The diagnostic uses of saliva, J. Oral Pathol. Med. 19 (1990) 119–125], it is now meeting the demand for inexpensive, non-invasive and easy-to-use diagnostic aids for oral and systemic diseases, drug monitoring and detection of illicit use of drugs of abuse, including alcohol. As the salivary secretion is a reflex response controlled by both parasympathetic and sympathetic secretomotor nerves, it can be influenced by several stimuli. Moreover, patients taking medication which influences either the central nervous system or the peripheral nervous system, or medication which mimic the latter as a side effect, will have an altered salivary composition and salivary volume. Patients suffering from certain systemic diseases may present the same salivary alterations. The circadian rhythm determines both the volume of saliva that will and can be secreted and the salivary electrolyte concentrations. Dietary influences and the patient's age also have an impact on composition and volume of saliva. The latter implies a wide variation in composition both inter- and intra-individually. Sampling must therefore be performed under standardized conditions. The greatest advantage, when compared to blood sample collection, is that saliva is readily accessible and collectible. Consequently, it can be used in clinically difficult situations, such as in children, handicapped and anxious patients, where blood sampling could be a difficult act to perform.     

唾液中滥用药物分析及其与血液中药物浓度的相关性

唾液是一种成分简单、易于采集的体液,某些药物在唾液中的浓度可以反映其血药浓度。本文分析了滥用药物进入唾液的机制和影响因素,综述了唾液中滥用药物分析时样品的采集、前处理和检测方法以及唾液与血液中药物浓度的相关性。认为唾液是临床和法医学方面很有价值的分析样品,用唾液中滥用药物浓度来推测血药浓度具有一定的法医学意义。     

Detection of drugs in saliva of impaired drivers

This study examined the feasibility of detecting drugs using saliva samples obtained from impaired drivers. Screening procedures on 1- to 2-mL samples were for cannabinoids, volatiles, benzodiazepines, and other acidic/neutral/basic drugs. Methodology consisted of enzyme multiple immunoassay technique (EMIT) and temperature programmed gas chromatography with confirmation by gas chromatography/mass spectrometry (GC/MS). Fifty-six samples were obtained from drivers arrested for suspicion of impaired driving. Other than alcohol, the major drugs detected were cannabinoids and diazepam. Cocaine was found in one case.     

UPLC-MS/MS测定唾液中的3种毒品成分

目的建立了超高效液相色谱-串联质谱法同时检测唾液中的甲基苯丙胺、氯胺酮和吗啡成分。方法唾液样品经沉淀蛋白后,通过ACQUITY UPLC BEH Phenyl(100mm×2.1mm,1.7μm)色谱柱分离,以0.3%甲酸水和乙腈作为流动相进行梯度洗脱,采用电喷雾离子源正离子(ESI+)多反应监测(MRM)模式进行质谱分析。结果甲基苯丙胺、氯胺酮和吗啡在4μg/L^20μg/L质量浓度范围内线性关系良好;在4μg/L、10μg/L、50μg/L、100μg/L、200μg/L五组添加样本下,添加回收率范围在87%~128%;甲基苯丙胺、氯胺酮、吗啡的检出限(LOD)和定量限(LOQ)均分别为0.2μg/L和4μg/L。结论本方法采用乙腈沉淀蛋白提取,快速、简单、回收率高,适用于同时检测唾液中甲基苯丙胺、氯胺酮和吗啡。     

Review: Pharmacokinetics of illicit drugs in oral fluid

This article reviews studies that have measured drug concentrations in oral fluid following controlled dosing regimens. A total of 23 studies have been identified over the last 15 years. These show that the amphetamines including designer amphetamines, cocaine, cannabis and cocaine are quickly found in oral fluid following dosing and usually have similar time-courses to that in plasma. Following common doses peak oral fluid concentrations exceed 0.1 microg/mL and often even 1 microg/mL. The drug concentration will depend on whether a dilution step occurs with buffer as part of the sampling procedure. The uses of collectors that stimulate oral fluid usually reduce the drug concentration compared to a non-stimulated manner. This reduction will not disadvantage the recipient since it will potentially reduce the detectability of drug in oral fluid compared to non-stimulated collections. Only one recent study has been reported for a benzodiazepine. This showed nanogram per milliliter concentrations for flunitrazepam. More studies are required for benzodiazepines and indeed for other drugs, particularly in multiple drug situations and where disease may affect the pharmacokinetics of drugs.     

Review: Pharmacokinetics of illicit drugs in oral fluid

This article reviews studies that have measured drug concentrations in oral fluid following controlled dosing regimens. A total of 23 studies have been identified over the last 15 years. These show that the amphetamines including designer amphetamines, cocaine, cannabis and cocaine are quickly found in oral fluid following dosing and usually have similar time-courses to that in plasma. Following common doses peak oral fluid concentrations exceed 0.1 μg/mL and often even 1 μg/mL. The drug concentration will depend on whether a dilution step occurs with buffer as part of the sampling procedure. The uses of collectors that stimulate oral fluid usually reduce the drug concentration compared to a non-stimulated manner. This reduction will not disadvantage the recipient since it will potentially reduce the detectablity of drug in oral fluid compared to non-stimulated collections. Only one recent study has been reported for a benzodiazepine. This showed nanogram per milliliter concentrations for flunitrazepam. More studies are required for benzodiazepines and indeed for other drugs, particularly in multiple drug situations and where disease may affect the pharmacokinetics of drugs.     

Technology transfer into capital-intensive industry: I. The paper industry by the year 2000

Traditionally, new technology has been slow to enter the paper industry, which turns over its capital stock in about 40 years. In this paper, we will examine some of the reasons for this long transition period and the implications of such a transition period for government policy. If the turnover time could be cut in half, the potential energy savings could be 4 quadrillion Btu (Quads) in 20 years. Examples of new technologies that will become prominent throughout the paper industry by the year 2000 include vapor recompression evaporation, oxygen bleaching, twin-wire forming and extended nip pressing. We present explicit projections of production shares (based on a computer model) for selected new technologies. New technology blends into an industry over a period of years. This paper examines some of the factors that accelerate or retard this transition in the capital-intensive (“heavy”) industries. For purposes of this article, our example is the paper industry, and so the examples of new innovations are drawn from pulp and paper-making processes. (Incidentally, we use the term “paper” throughout as a shorthand for SIC 26, Pulp, Paper and Paperboard.) The examination of paper-industry technology reported here is based to a great extent on a study of industrial energy use [1] conducted by the Office of Technology Assessment (OTA) for the U.S. Congress. The OTA study examined the four most energy-intensive American industries (paper, steel, chemicals and petroleum refining), to identify technologies to improve energy efficiency, to project industrial energy use in each industry between now and the end of the century, and to assess the impact of various policies on energy use and energy efficiency. The study found remarkable similarities between the four industries. One notable commonality is the attitude of management towards introduction of new technology.     

唾液检材在毒品检测中的应用

近年来,毒品滥用问题日益突出,提高生物样品中毒品检测技术的性能是法庭毒物学研究的重点。相比于血液和尿液样品,唾液在的样品采集和毒品检测中具有诸多优势,因而逐渐受到重视。本文对近年来国内外唾液样本用于毒品检测方面的研究成果进行综述,介绍唾液毒品检测的发展情况以及相关的代谢动力学研究状况,旨在为相关研究和实践提供参考。     

Determination of phenotypes of salivary amylase in liquid saliva and saliva stains

An isoelectric focusing method is described for typing salivary amylase in liquid saliva and saliva stains. The estimated gene frequencies in a British population, calculated on the basis of three alleles operating at a single locus, were Amy 1, 0.909; Amy 2, 0.065; Amy 3, 0.026. This system may be useful in forensic investigations.     

Ultra-trace analysis of illicit drugs from transfer of an electrostatic lift

This article introduces a method of collecting and analysing drug residues that integrates both electrostatic lifting and nanomanipulation-coupled to nanospray ionization mass spectrometry. The application of this hyphenated technique exhibits a useful means of collection and extraction of drug residues with ease and efficiency along with decreased limits of detection. From this method, it will be shown how increased sensitivity of analysis and lower limits of detection for drug analysis can be achieved. The same principles that allow lifting of dust prints by electrostatic lifting can be applied to lifting drug residues. Probing of the drug residues by nanomanipulation occurs directly from the lift, which provides a great platform for extraction. Nanomanipulation-coupled to nanospray ionization-mass spectrometry has been used for the extraction of trace analytes in previous experiments and is known as a very sensitive technique for the detection of ultra-trace residue. This method will demonstrate the electrostatic lifting of drug residue particles from a surface followed by extraction and ionization with nanomanipulation-nanospray ionization. The utility of this novel methodology allows for a more productive analysis when presented with ultra-trace amounts of sample.     

Technology transfer perspectives in globalising India (drugs and pharmaceuticals and biotechnology)

The paper briefly outlines the status of technology transfer related issues in drugs & pharma and biotechnology sectors in India. The paper also outlines the contemporary business strategies including R&D and technology transfer models. The study indicates that present technology transfer policies and mechanisms are weak and need to be restructured. The current fiscal incentives and tax concessions etc. available for R&D in industry seem to have outlived and are no longer attractive because of continuous lowering of tariff rates and tax rates in the context of WTO and liberalization of policies. Moreover, the issue of R&D support to industry is not covered in the WTO as in case of subsidies. Therefore, it is advisable for the government to revisit the existing promotional measures for R&D. FDI policies also need to be tailored to encourage Technology transfers and capability building. Recommendations are made for making Technology Transfer more effective for the growth and competitiveness of the industry. A technology transfer management model is suggested.      

Making drugs available at affordable prices: how universities' technology transfer offices can help developing countries

Legal context: In recent years, the prices at which medicines are soldin, and to, developing countries has become a hot politicalsubject affecting the international pharmaceutical industry.Specific legislative measures have followed the political debate,including (1) the EU Regulation 816/2006 on ‘compulsorylicensing of patents relating to the manufacture of pharmaceuticalproducts for export to countries with public health problems’and (2) the The Doha Declaration adopted by the Fourth MinisterialConference of the World Trade Organisation (WTO) in 2001, andthe subsequent Decisions by the WTO General Council to implementthe Declaration in August 2003 and to amend the TRIPs (Trade-RelatedAspects of Intellectual Property Rights) Agreement in December2005. Universities are increasingly considering whether to includeterms in their licence agreements with pharmaceutical companiesthat address this issue. Key points and practical significance: Universities may wish to consider whether it is part of theirmission to negotiate special terms in licence agreements tobenefit the developing world. Where universities decide that,in principle, they wish to include ‘humanitarian-licensing’clauses in their licence agreements, they need to find a formof words that is likely to achieve their objectives and be acceptableto pharmaceutical industry licensees. This article considerssome of the options and suggests some specimen wording.     

The dynamics of illicit drugs production: Future sources and threats

This paper examines the opportunities for illicit drugs production which arise out of the economic, political and social conditions of some countries. These drivers can help us to understand the geographical pattern of global drugs sources and assist in the process of identifying those parts of the world in which new production opportunities are arising. It was found that there is not a homogenous set of risks which contributes to drugs production. Instead, the particular contexts which are conductive to drug production activities varies for different drug types. This has influenced the different patterns of drugs production for highly refined, organic drugs, such as cocaine and heroin, compared to synthetic drugs. The nature of developments which could trigger new areas of drug production are discussed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Regulation of technology transfer: The Mexican experience

Beginning some 20 years ago, regulation of technology transfer became common-place in a number of developing countries. Whether such regulation could prove beneficial was often questioned, particularly in the industrialized world. But with a 15–20 year history to study, we can now look at the impact that regulation has had. Mexico presents a good case study, as its original law was one of the earliest, and the country's political continuity has led to a detectable evolvement of the technology-transfer process that allows analysis of various factors over time.     

The sensitivity and specificity of red-starch paper for the detection of saliva.

The detection of saliva in forensic casework is extremely important in many types of cases. This study describes a relatively sensitive method, based on a red dye bound to starch, for the detection of amylase. The sensitivity and specificity of the method has been examined by testing over 50 household products, various body fluids and five laboratory chemicals. This study demonstrated for the first time that positive results can be obtained from certain washing powders as well as other household products. As well as detecting amylase in saliva, positive Red-Starch results were obtained from faeces and urine. The method was found to be suitable for the detection of mixtures of saliva and semen in conjunction with the Brentamine test for the detection of acid phosphatase.     

Isolation of deoxyribonucleic acid (DNA) from saliva and forensic science samples containing saliva.

Saliva and saliva-stained materials were examined as potential sources of deoxyribonucleic acid (DNA) for DNA analysis and identity testing. In this paper, the authors demonstrate that DNA was isolated and DNA banding patterns suitable for DNA typing were obtained from fresh saliva and various saliva-stained materials, such as envelopes, buccal swabs, gags, and cigarettes. Furthermore, DNA and DNA banding patterns were obtained from actual forensic evidentiary samples containing mixed saliva/semen stains. The DNA banding patterns obtained from saliva or saliva-stained material were indistinguishable from the patterns obtained from blood or hair from the same individual. Intact DNA was readily isolated and DNA banding patterns were obtained from saliva stored at -20 degrees C and dried saliva stains stored under varying conditions. We conclude that saliva and saliva-stained material can be good sources of DNA for analysis and for DNA typing in certain forensic settings.