Drugs In Body Fluids Research Articles

A carrier free delivery system of a MAGL inhibitor is effective on ovarian cancer

Monoacylglycerol lipase (MAGL) is a promising target for cancer therapy due to its involvement in lipid metabolism and its impact on cancer hallmarks like cell proliferation, migration, and tumor progression. A potent reversible MAGL inhibitor, MAGL23, has been recently developed by our group, demonstrating promising anticancer activities. To enhance its pharmacological properties, a nanoformulation using nanocrystals coated with albumin was prepared (MAGL23AF). In a previous work, the formulated inhibitor showed potency in ovarian and colon cancer cell lines in terms of IC50, and was tested on mice in order to assess its biocompatibility, organs biodistribution and toxicity. In the present work, we expanded the investigation to assess the potential in vivo application of MAGL23AF. Stability assays in serum and in human derived microsomes showed a good structural stability in physiological conditions of MAGL23AF. The antitumor efficacy tested on mice bearing ovarian cancer tumor xenografts demonstrated that MAGL23AF is more potent than the non-formulated drug, leading to necrosis-driven cancer cell death. In vivo studies revealed that albumin-complexed nanocrystals improved the therapeutic window of MAGL23, exhibiting a favorable biodistribution with slightly increased accumulation in the tumor. In conclusion, the MAGL23AF showed increased in vitro stability in conditions mirroring the bloodstream environment and hepatic metabolism coupled with an optimal antitumor efficacy in vivo. These results not only validates the efficacy of our formulation but also positions it as a promising strategy for addressing challenges related to the solubility of drugs in body fluids.

Intrinsic Dual-Emitting Carbon Quantum-Dot-Based Selective Ratiometric Fluorescent Mercaptopurine Detection.

Mercaptopurine (6-MP), an immunosuppressive drug, has been widely prescribed for treating leukemia and autoimmune diseases. The level of the 6-MP drug in body fluids is of great interest due to the severe health problems related to its overdose. This study used a facile microwave preparation route to synthesize carbon quantum dots (CQDs) using glutathione and formamide as carbon sources. The obtained monodispersed quantum dots showed dual fluorescence emission with a sensitive affinity toward the 6-MP drug. The sensor's response was optimized by tuning the temperature, pH, and volume ratio of the probe. The prepared ratiometric fluorescence method showed accurate measurements for determining mercaptopurine in aqueous solutions in the concentration range of 1.4-7.6 mg L-1 with the limit of detection of 1.3 mg L-1. The sensor's performance was assessed in complex solutions, human urine, and human plasma sample and recovery values in the range of 88-127% were obtained. The reliable dual fluorometric sensor showed promising results for 6-MP determination and potential application for the determination of other chemical and biochemical species.

A simple single jar "on-off fluorescence" designed system for the determination of mitoxantrone using an eosin Y dye in raw powder, vial, and human biofluids.

In this work, a direct, simple, one-pot, and green spectrofluorimetric approach was applied to measure mitoxantrone, a chemotherapeutic agent, through a green validated method. The suggested approach focused on establishing an easy association complex combining mitoxantrone and the eosin Y reagent in a slightly acidic solution. The fluorometric analysis was dependent on off-mitoxantrone action on the emission intensity of the dye (eosin Y) at 544.5 nm (excitation = 301 nm). The devised system has a linear range of 0.07–2.5 μg mL−1 and a detection limit of 0.016 μg mL−1. All system parameters for the formation of mitoxantrone–eosin Y complexes were modulated analytically. Also, the system was reviewed in agreement with ICH criteria. Furthermore, the proposed model was approached to quantify mitoxantrone in its pharmaceutical vial dosage form with high recoveries. Also, the proposed spectroscopic design was efficiently employed to detect the investigated drug in body fluids (blood and urine). Lastly, the designed method was evaluated from a greenness point of view according to eco-scale.

A colorimetric immuno-microarray for the quantitation and direct visualization of illicit drugs in body fluids.

The design and testing of integrated colorimetric microarray immunochips (immuno-microarrays) are reported for the quantitation and direct visual determination of multiple illicit drugs (e.g., morphine, cocaine and amphetamine) in body fluids. Such an immuno-microarray platform utilizes a competitive immunoassay format, which is based on silver staining for quantitative detection and multicolor staining for direct visualization (i.e., qualitative identification) of analytes present in the sample. Under optimized conditions, the dynamic response ranges of 3.7-1000, 1.1-300 and 1.5-300 ng mL-1 were achieved for amphetamine, cocaine, and morphine, respectively, which are wider towards low concentrations than those of standard enzyme-linked immunosorbent assay (ELISA) tests. The limits of detection (LODs) for morphine, cocaine, and amphetamine were determined to be 1.5 ± 0.1, 1.1 ± 0.1 and 3.7 ± 0.2 ng mL-1, respectively in oral fluids, which meet government regulations for law enforcement. The obvious advantages of multiplexing, simultaneous visual recognition, and accurate quantitation make the on-site detection feasible, confirming that such a colorimetric immuno-microarray holds promise for practical applications.

Determination of Amphetamine and Methamphetamine in Human Hair by Gas Chromatography Mass Spectrometry

This article develops a combined solid phase extraction (SPE) and gas chromatography – mass spectrometry (GC-MS) procedure for determining amphetamine-type stimulants Amphetamine (AM) and Methamphetamine (MA) in human hair. Hair samples were incubated in methanol containing 1% hydrochloric acid in 18 hours and then subjected to SPE. The obtained extracts were evaporated to dryness, derivatized with heptafluorobutyric anhydride (HFBA) at 70 °C for 30 minutes prior to GC–MS analysis. Gas chromatography mass spectrometry was run on HP5-MS column (30 m × 0.25 mm × 0.25 µm) with detector MS 5975C. Experimentally, the proposed method proved sensitive, simple and time-saving, but quite accurate with a low limit of detection (LOD = 0.05ng/mg) and quantitation (LOQ = 0.15ng/mg).
 Keywords:
 SPE, GC – MS, hair samples, amphetamine, methamphetamine.
 References
 [1] Ming-Ren Fuh, Ti-Yu Wu and Tzuen-Yeuan Lin, Determination of amphetamine and methamphetamine in urine by solid phase extraction and ion-pair liquid chromatography–electrospray–tandem mass spectrometry Talanta, 68 (3) (2006), 987-991. https://doi.org/10.1016/j.talanta.2005.06.057[2] Naresh C. Jain, Thomas C. Sneath, and Robert D. Budd, Rapid Gas-Chomatographic Determination of Amphetamine and Methamphetamine in urine, Clinical Chemistry, 20 (11) (1974) 1460-1462. https://doi.org/10.1093/clinchem/20.11.1460.[3] Dong-liang Lin, Rea-Ming Yin, Ray H. Liu, Gas Chromatography-Mass Spectrometry (GC-MS) Analysis of Amphetamine, Methamphetamine, 3,4-Methylenedioxy- amphetamine and 3,4-Methylenedioxymethamphetamine in Human Hair and Hair Sections, Journal of Food and Drug Analysis, 13(2) (2005) 193-200. https://doi.org/10.38212/2224-6614.2526[4] María Jesús Tabernero, Maria Linda Felli, Ana María Bermejo, Marcello Chiarotti, Determination of ketamine and amphetamines in hair by LC/MS/MS, Anal Bioanal Chem, 395(2009), 2547–2557. https://doi.org/10.1007/s00216-009-3163-4.[5] D.V. Doan, D.Q. Huy, N.D. Hue, T.M. Tri, Determination of methamphetamine in urine samples by gas chromatography mass spectrometry combined with solid phase extraction technique, Journal of Science and Technology 47 (6) (2009) 53-58 (in Vietnamese).[6] Rodger L. Foltz, Allison F. Fentiman, Ruth B. Foltz, GC/MS Assays for Abused Drugs in Body Fluids, National Institute on Drug Abuse, Maryland, 1980.[7] AOAC, Appendix F: Guidelines for Standard Method Performance Requirements, AOAC official methods of analysis, Maryland, 2016.[8] Eunyoung Han, Martin P. Paulus, Marc Wittmann, Heesun Chung, Joon myong Song, Hair analysis and self-report of methamphetamine use by methamphetamine dependent individuals, Journal of Chromatography B, 879 (2011) 541–547. https://doi.org/10.1016/j.jchromb.2011.01.002.
 
 

ANALYTICAL METHODS FOR THE DETERMINATION OF HYDROXYCHLOROQUINE IN VARIOUS MATRICES

Hydroxychloroquine (HCQ) is classified under the class of drugs called antimalarials. This is used for preventions and treatment of malaria. HCQ is also used in the treatment of DLE (Discoid Lupus Erythematosus) or SLE (Systemic Lupus Erythematosus) and RA (Rheumatoid Arthritis). Recently, this drug attracts its attention by scientists of all of the worlds for its potential activity in the improvement of conditions of covid patients. There are many clinical trials are under process to prove its activity against this dangerous virus. The presented review describes different analytical procedures for the analysis of HCQ in various components available in the currently available literature. The paper will be certainly helpful for the scientists and researchers engaged in research, especially in the development of formulation or quality assurance of HCQ. The results of any clinical trial also includes the determination of drug in body fluids for interpretation of data. The analytical methods described here are explained in three parts; spectrophotometry, chromatography and other (including capillary electrophoresis and electroanalytical methods)

Sub-Parts-per-Trillion Level Detection of Analytes by Superhydrophobic Preconcentration Paper Spray Ionization Mass Spectrometry (SHPPSI MS).

A new kind of ambient ionization method named superhydrophobic preconcentration paper spray ionization mass spectrometry (SHPPSI MS) is introduced, where superhydrophobicity and paper spray mass spectrometry (PS MS) are coupled. The SHPPSI MS requires only microliter amounts of analyte solutions, allows easy sampling procedure, and provides high sensitivity for a diverse array of analytes. It can be used to detect food adulteration at extremely low concentrations. The experimental methodology involves modifying one of the surfaces of a triangularly cut filter paper to make it acquire low surface energy by drop casting a green and ecofriendly superhydrophobic coating material over it followed by drying. A micrometer scale defect was made at close proximity to one of the tips of the paper using a pin. Preconcentration of the sample was accomplished by allowing a 10 μL droplet of an aqueous solution of the analyte to stand at the defect followed by drying naturally. The dried paper was used as the substrate for paper spray mass spectrometry by eluting the analyte with a suitable solvent. This novel technique was used to detect melamine in adulterated milk, whose detection at the ppt level in milk normally needs sophisticated instruments, a larger amount of sample, and a complex sampling procedure, including further purification and separation. The SHPPSI MS detects melamine directly from milk at the sub-ppb level by simply putting a microdroplet of adulterated milk at the substrate and eluting the sample with methanol. This paper-based technique can be a promising tool for direct sensing of analytes such as drugs in body fluids, pesticides in water and soil, etc.

Surface modification of electrodes by carbon nanotubes and gold and silver nanoparticles in monoaminoxidase biosensors for the determination of some antidepressants

Surface modification of screen-printed graphite electrodes with nanostructured materials (multiwall carbon nanotubes, gold and silver nanoparticles) allow their application as supports of amperometric monoaminoxidase biosensors for the determination of antidepressant drugs (moclobemide, tianeptine, and amitriptyline). This approach improves analytical characteristics of the corresponding biosensors because of the inhibitory effect of antidepressants (two-parameter concerted inhibition) on the catalytic activity of an immobilized enzyme. The analytical capabilities of the developed biosensor types were compared. The range of working concentrations was from 5 × 10–9 to 1 × 10–4 M and the lower limit of the analytical range was of about 8 × 10–10 M. Biosensors based on electrodes modified with nanostructured materials were tested in the control of the concentration of drugs in body fluids (urine) and dosage forms.

Heroin Body Packer’s Death in Shiraz, Iran; a Case Report and Literature Review

Background: Intra-corporeal concealment of illicit drugs known as ‘body packing’ is uncommonly reported. These drugs mainly comprise opium, heroin, cocaine, 3,4-methylenedioxymethamphetamine (ecstasy), amphetamines, and marijuana or hashish. Body packers may also be called swallowers, internal carriers, couriers or mules. Although this practice is not new, its medical complications have always been a matter of concern. Some have reported improved packaging methods to deal with such complications. Body packing is an on-going drug smuggling method and authorities across the world are always on the alert. Case Presentation: It has reported a case of death due to the effects of heroin concealed in a man who was attempting to smuggle the drug within his gastro-intestinal track. According to forensic procedure of sudden unnatural death, the decedent had to accept a series of examination such as CT scan, autopsy and toxicological analysis. He was found dead from acute heroin intoxication due to the rupture of drug packet in the stomach. Discussion: This case illustrates the challenges to forensic diagnosis in forensic medical methods in evaluation of potential drug packers and therefore it needs to consider all methods and finally best method involved in forensic diagnosis. Conclusion: In conclusion, in body packer’s postmortem pathological signs are combined with evidence of the presence of drug pellets in the body as well as toxicological analysis in the ante-mortem history, and clinical reports. Toxicological analysis of the presence of the drug in body fluids, such as plasma, and in tissue extracts may not be of value when the level of the drug decreases after a period of metabolism.

Poly-N-acryloyl-(l-phenylalanine methyl ester) hollow core nanocapsules facilitate sustained delivery of immunomodulatory drugs and exhibit adjuvant properties.

Polymeric hollow nanocapsules have attracted significant research attention as novel drug carriers and their preparation is of particular concern owing to the feasibility to encapsulate a broad range of drug molecules. This work presents for the first time the synthesis and development of novel poly-N-acryloyl l-phenylalanine methyl ester hollow core nanocapsules (NAPA-HPNs) of avg. size ca. 100-150 nm by the mini-emulsion technique. NAPA-HPNs are biocompatible and capable of encapsulating sodium nitroprusside (SNP) at a rate of ∼1.3 μM per mg of capsules. These NAPA-HPNs + SNP nano-formulations maintained homeostasis of macrophages which carry and facilitate the action of various drug molecules used against various diseases. These NAPA-HPNs also facilitate the prolonged release of a low level of nitric oxide (NO) and enhance the metabolic activities of pro-inflammatory macrophages, which are important for the action of various drugs in body fluids. NAPA-HPN mediated skewing of naïve macrophages toward the M1 phenotype potentially demonstrates its adjuvant action on the innate immune system. These results potentially suggested that NAPA-HPNs can serve both as a carrier of drugs as well as an adjuvant for the immune system. Thus, these nanocapsules could be used for the effective management of various infectious or tumor diseases where immune-stimulation is paramount for treatment.

A new version of hydrophilic interaction liquid chromatography with the use of ionic liquids based on imidazole for the determination of highly polar drugs in body fluids

A possibility of using ionic liquids based on imidazolium as modifiers of the mobile and stationary phases under the conditions of reversed-phase and hydrophilic chromatography ( HILIC ) for the separation of polar biologically active substances (amino acids, vitamins and drugs) has been investigated. It was shown that the introduction of imidazolium ionic liquids ( IL ) to the eluent led to the dynamic modification of the C18 sorbent surface which in turn led to the increased efficiency and selectivity of basic analytes separation. The realization of HILIC mode was possible due to the formation of a hydrophilic coating. Influences of the alkyl radical (C 4 , C 6 , C 8 , C 12 ) length, nature of the counterion (Cl - , BF 4 - ), IL concentration (0.1 - 20 mM), pH of the mobile phase and concentration of organic additive on the efficiency and selectivity of the separation of polar drugs had been studied. In addition, the ability of cetyltrimethylammonium bromide ( CTAB ) to provide HILIC conditions in the concentrations lower than critical micelle concentration ( CMC ) has been investigated. The possibility of determining drugs ( p- aminosalicylic acid and antibiotics levofloxacin, sparfloxacin) in blood plasma under HILIC conditions was shown. Key words: highly polar drugs, water-soluble vitamins, hydrophilic chromatography, ionic liquids DOI: http://dx.doi.org/10.15826/analitika.2017.21.3.004 V.D. Somova, E.A. Bessonova, L.A. Kartsova Saint Petersburg State University, 7/9 Universitetskaya nab., St. Petersburg, 199034, Russian Federation

Dispersive liquid-liquid microextraction combined with acetonitrile stacking through capillary electrophoresis for the determination of three selective serotonin reuptake inhibitor drugs in body fluids.

Dispersive liquid-liquid microextraction was combined with acetonitrile stacking in capillary electrophoresis for the identification of three selective serotonin reuptake inhibitors (citalopram, fluoxetine, and fluvoxamine) in human fluids such as urine and plasma. Parameters that affect the extraction and stacking efficiency, such as the type and volume of the extraction and disperser solvent, extraction time, salt addition for dispersive liquid-liquid microextraction, and sample matrices, pH, and concentration of the separation buffer for stacking, were investigated and optimized. Under optimum conditions, the enrichment factors were in the range of 1195-1441. Limits of detection ranged from 1.4 to 1.7 nM for the target analytes. Calibration graphs displayed satisfied linearity with R2 greater than or equal to 0.9978, and relative standard deviations of the peak area analysis were in the range of 2.9-5.0% (n = 3). The recoveries of all tricyclic antidepressant drugs from urine and plasma were in the range of 77-117 and 79-106%, respectively. The findings of this study show that dispersive liquid-liquid microextraction acetonitrile-stacking capillary electrophoresis is a rapid and convenient method for identifying tricyclic antidepressant drugs in urine and plasma.

Sensitivity enhancement in direct coupling of supported liquid membrane extractions to capillary electrophoresis by means of transient isotachophoresis and large electrokinetic injections

Enhanced sensitivity for determination of basic drugs in body fluids was achieved by in-line coupling of extraction across supported liquid membrane (SLM) to large electrokinetic injection and transient isotachophoresis-capillary zone electrophoresis (tITP-CZE) in commercial CZE instrument. Twelve cm long tITP plug of 300mM ammonium acetate was formed in the separation capillary just before the electrokinetic injection of acceptor solution containing nortriptyline, haloperidol and loperamide extracted across the SLM. The tITP plug ensured efficient stacking and preconcentration of the injected basic drugs due to the tITP action of ammonium and the drugs were then separated by CZE using 5.2M acetic acid as background electrolyte. No interferences were observed from highly-abundant body fluid species (NaCl and human serum albumin) due to the excellent clean-up properties of SLMs and analytical sensitivity increased up to 340 times compared to SLM extractions coupled in-line to CZE with standard hydrodynamic injections. The SLM-tITP-CZE method was characterized by good repeatability (RSDs of peak areas below 7.8%), linearity over two orders of magnitude (r2 better than 0.994) and limits of detection (defined as 3×S/N) between 3 and 45μg/L. Interfacing of SLM extractions to CZE instrumentation was achieved by low-cost, disposable micro-extraction devices, which can be routinely prepared in every analytical laboratory. These devices eliminated sample carry-over, minimized the need for manual sample handling and ensured fully automated determination (including extraction, injection, preconcentration and separation) of the three basic drugs in 20μL of untreated body fluids.

Detection of Poisons, Pollutants, Narcotics, and Drugs in Water Using Excitation–Emission Spectroscopy Without Added Reagents

This article presents an optical photoluminescence spectroscopic method for the qualitative and quantitative detection of impurities, hazardous materials, pesticides, and pollutants in water. In addition, it lays the groundwork for the development of a potential application to detect, without added reagents, drugs in body fluids. Based on synchronous fluorescence spectroscopy of organic aromatic compounds—specifically, polycyclic aromatic hydrocarbons—the method entails simultaneously monitoring the excitation and emission spectra of the compounds. The full excitation and emission matrix thus generated provides 2D and 3D fluorescence maps of the tested sample. Diagonals through the map origin of the axes provide the synchronous fluorescence spectra at constant, measurable differences between the emission and excitation wavelengths, thus enabling the identification of multiple components. The map, a unique “fingerprint” of the sample, contains all its relevant spectroscopic information and enables very specific and accurate identification of the compounds and their components. Matching between database spectra, the calibration curves of standards and the spectra and the calibration curves from the samples enable accurate identification and quantification of the targeted analyte. The advantages of this method include its sensitivity (detection limits at ppm levels), accuracy, and simplicity of operation. In addition, the spectrometer (the Fluo-Imager prototype) is simple to operate and its maintenance costs are low. The design and performance of the spectrometer, the development of its corresponding software, the analysis of poisons (organic compounds) and their mixtures in water, and our preliminary studies of drugs in body fluids are discussed in this paper.

Coupling Micropipette Tipbased Microextraction with Desorption Corona Beam Ionization Mass Spectrometry for Rapid Analysis of Antihypertensive Drugs in Body Fluid

Coupling Micropipette Tipbased Microextraction with Desorption Corona Beam Ionization Mass Spectrometry for Rapid Analysis of Antihypertensive Drugs in Body Fluid

Development of carbon-nanotube-assisted electromembrane extraction in the two-phase mode combined with GC for the determination of basic drugs

In this work, carbon-nanotube-assisted electromembrane extraction in the two-phase mode combined with GC was developed for the preconcentration and determination of basic drugs in body fluids. The multiwalled carbon nanotubes dispersed in organic solvent are held in the pores of the porous fiber wall by capillary forces and sonification. The membrane with immobilized carbon nanotubes acts as a sorbent and provides an additional pathway for analyte transport. This study demonstrates that the immobilization of carbon nanotubes in the supported liquid membrane is an excellent approach to enhance the performance of the extraction. Optimization of the variables affecting this method was carried out in order to achieve the best extraction efficiency. Optimal extractions were accomplished with octanol as the extraction solvent, 50 V as the driving force and pH 7.4 in the sample solution with the whole assembly agitated at 1000 rpm for 20 min. Under the optimized extraction conditions, the proposed technique provided good linearity (R(2) > 0.9990), repeatability (3.5-3.8%), low LODs (1.5 ng/mL), good preconcentration factors (292-316) and high recoveries (80-87%). Finally, this method was successfully used for the determination of tramadol and methadone in different body fluids including plasma and urine samples.

Direct detection of trace level illicit drugs in human body fluids by probe electrospray ionization mass spectrometry (PESI-MS)

Detection of illicit drugs by ambient mass spectrometry has been gaining attention due to the unique advantage of detecting trace levels of chemicals from complex matrices without or with minimal sample pretreatment. This paper reports the application, characteristics and advantages of probe electrospray ionization mass spectrometry (PESI-MS) for rapid, sensitive and direct detection of methamphetamine, morphine, cocaine and codeine from human urine, oral fluid and plasma. The limits of detection (LODs) of various illicit drug standards were found to be 2–5 ppb and the trace levels of drugs were confirmed by their exact masses obtained using an ‘Exactive Orbitrap’ mass spectrometer. Here, for the first time, we evaluate the quantitative capabilities of PESI-MS from urine, oral fluid and plasma using methamphetamine as a representative illicit drug and N-benzylmethylamine as an internal standard. The LODs for illicit drugs in body fluids were one to two orders of magnitude higher compared to the standard samples and the relative standard deviations for the quantitative analysis were found to be less than 20%. As PESI is a solid needle based ambient electrospray system and free from clogging problems, it can easily be used as a spraying and direct ionization source for complex liquid mixtures.

Arrays of SnO2 nanorods as novel solid phase microextraction for trace analysis of antidepressant drugs in body fluids

The arrays of tin oxide nanorods-solid phase microextraction (ATN-SPME) fibre coupled with the high performance liquid chromatography (HPLC) method was developed for simultaneous determination of selective serotonin reuptake inhibitors (SSRI), citalopram and fluoxetine, in human urine and plasma samples. The variables of interest in the Direct-SPME (D-SPME) were extraction time, pH, ion strength or salt percentage and desorption time of analytes from the fibre. These factors were optimised by using a Box-Behnken design and the response surface equations were developed. The optimal experimental conditions obtained from this statistical evaluation included: the salt percentage (30%, w/v), NaOH volume (6.5 μl from a 1 M solution), extraction time (10 min) and desorption time (30 min) for drugs in the plasma sample and The salt percentage (30%, w/v), NaOH volume (100 μl from a 1 M solution), extraction time (18 min) and desorption time (23 min) for drugs in the urine sample. A satisfactory reproducibility for the extraction from urine and plasma samples (R.S.D.<10%) was obtained. The linearity for urine and plasma ranged from 1 to 5×10(5) ng ml(-1) with a detection limit of 0.2 ng ml(-1) for citalopram and 0.5 ng ml(-1) for fluoxetine, which covered the typical urinary concentrations obtained for citalopram and fluoxetine.

Application of Nanotechnology in Traditional Chinese Medicine

Nanomedicine is the medical application of nanotechnology and related research. Application of nanotechnology in the research of traditional Chinese medicine (TCM) may be an important direction towards its modernization. This paper reviews literatures on nano-TCM which were published in the past decade. In accordance with the different carriers, four types of nano-TCM, nanoliposome, solid lipid nanoparticle, nanocapsule and polymer micelle are analyzed. Most nano-TCMs are performed on nanoliposome for its easy preparation, convenience for application and multi-purpose administrations. Because of their characteristics of slow-release, targeting, toxicity etc., solid lipid nanoparticles are used mainly for the package of insoluble drugs as carriers for intravenous injection or local administration for the purpose of targeted or controlled release. Carrying drugs by natural or synthetic polymer material, nanocapsules can promote the drug through the blood-brain barrier and enhance drug's bioavailability. Polymer micelle, a new type of nanoparticle developed in recent years, can increase the solubility of hydrophobic drugs in body fluid and extend drug duration. Nanotechnology is conducive to the development of Chinese medicine in many ways, but there are many problems that need to be solved. Application of nanotechnology in the complex system of TCM is still in the initial stage, innovations of theory and technology are worth the wait to promote the nano-TCM into the practical stage. Keywords: Nanotechnology, nano-TCM, nanoliposome, solid lipid nanoparticle, nanocapsule, polymer micelle, efficacy

Accelerator mass spectrometry in the attomolar concentration range for14C-labeled biologically active compounds in complex matrixes

Accelerator mass spectrometry (AMS) is an ultra-sensitive analytical method suitable for detection of sub-nanomolar concentrations of labeled biological substances such as pharmaceutical drugs in body fluids. A limiting factor in extending the concentration measurements to the sub-picomolar range is the natural 14C content in living tissues. This can be circumvented by separating the labeled drug from the tissue matrix with, for example, liquid chromatography. The analysis of drugs and their metabolites or endogenous compounds in biological fluids by liquid chromatography is usually complicated and the sample preparation step remains the most serious problem both with regard to losses and degradation of the analyte, and also automation of the analysis. In this article a method for detection and quantification of extremely low concentrations of 14C-labeled biomolecules in biological fluids by AMS is described. The use of a column switched chromatographic system incorporating a restricted-access media (RAM) column allowed the direct injection of untreated human plasma samples, which reduces the total time of analysis and makes automation of the sample preparation step possible. As the separated total drug amount is in the attogram to femtogram region, it is not possible to use a standard AMS sample preparation method, where mg sizes are required. We have utilized a sensitive carbon carrier method where a 14C-deficient compound is added to the HPLC fractions and the composite sample is prepared and analysed by AMS. The method shows remarkable sensitivity, low background values and good linearity, allowing the detection and quantification of a pharmaceutical drug in human plasma in the low femtomolar and down to the attomolar concentration range.