WO2022097126A1

WO2022097126A1 - Voltage-enhanced micro extraction of anti-aids drugs on nano-adsorbent octa decyl silica

Info

Publication number: WO2022097126A1
Application number: PCT/IB2021/062043
Authority: WO
Inventors: Faezeh GHASEMIZADEH TAMAR; Saba BEHROUZNIA
Original assignee: Ghasemizadeh Tamar Faezeh; Behrouznia Saba
Priority date: 2021-12-20
Filing date: 2021-12-20
Publication date: 2022-05-12

Abstract

A method for the fabrication of solid-phase micro extraction (SPME) fiber by covalent bonding of Nano-ODS adsorbent on a stainless steel wire by sol-gel method. The fabricated SPME fiber is then used in the EEDI-SPME-HPLC-UV method for separation, extraction and pre-concentration of antidiabetic drugs zidovudine and lamivudine in biological fluids of the human body.

Description

Voltage-enhanced micro extraction of anti-AIDS drugs on Nano-adsorbent octa decyl silica

In this invention, Nano-ODS adsorbent was first synthesized and deposited on a stainless steel wire with covalent bonding by sol-gel method. The covalent bonding of the adsorbent and the substrate makes the adsorbent stronger in the DI-SPME method and eliminates the problems compared to many commercially made fibers. This fiber was then used in EE-DI-SPME-HPLC-UV method to extract and measure AIDS drugs. A new solid phase micro extraction fiber (SPME) was fabricated by covalent bonding of octa-decyl silica (Nano-ODS) nanoparticles on a stainless steel wire surface. This fiber is very efficient and durable, and due to its greenness, low cost and simplicity of preparation method, it can enter the commercialization phase.

Impregnating or coating (B01J 20/32) - Investigating or analyzing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography (G01N 30/00)

Fiber coating in SPME plays an important role in extraction efficiency, so that the main factor affecting the analyte distribution constant between the sample matrix and the fixed phase. In SPME methods, the physical and chemical properties of the fiber adsorbent have a great impact on the overall extraction performance, including sensitivity, selectivity and reproducibility of the method. In recent years, nanomaterials due to their high porosity, which improves the speed and efficiency of extraction, remarkable thermal, mechanical and chemical stability in extraction methods have received much attention. Silica is widely used in research and industry due to its abundance, cheapness, numerous surface modification methods, high porosity and adsorption power, and non-toxicity. The most important applications of silica are the preparation of adsorbents and chromatographic columns. Large sums of money are spent annually on the production and improvement of the performance of these chromatographic columns. But silica surface modification is a multi-step process that involves a variety of complex methods. The sol-gel method is usually used to cover or modify the surface of compacted silica.

In 1987, Y. Guo and colleagues used sol-gel technology to create stationary phases in separation methods.

In 2020, Ghiasvand et al. Covered the inner wall surface of a chromatographic column with spherical silica nanoparticles using the dynamic nucleation method, then deposited the silica octadecyl chains (ODS) on the spherical silica nanoparticles using the reflux method.

In 2007, voltage applications were used to reinforce solid phase micro extraction methods.

Applying voltage to the desired absorber enhances the migration of the charged analyte to the absorber and thus increases the extraction efficiency. In order to increase this effect as much as possible (voltage application), new absorbers with high capacity, better selectivity and more electrical conductivity should be used than the absorbers used. In this invention, ODS nanoparticles with covalent bonding were used on the surface of a fiber (steel base) and by applying voltage, it was used for simultaneous measurement of anti-AIDS drugs zidovudine and lamivudine.

Solid-phase micro extraction coatings and methods for their preparation

United States Patent 8598325

There is described a coated solid phase micro extraction (SPME) fiber for use in direct immersion SPME of a food matrix that includes carbohydrates. The coated SPME fiber includes a SPME fiber for absorbing a small molecule from the food matrix; and a protective coating which has a surface that is substantially uniform and substantially smooth, the protective coating reducing adsorption of the carbohydrates onto the SPME fiber and allowing the SPME fiber to extract the small molecule from the food matrix. A process for producing the coated SPME fiber and a method of performing solid phase micro extraction are also described.

In this invention, ODS nanoparticles with covalent bonding were used on the surface of a fiber (steel base) and by applying voltage, it was used for simultaneous measurement of anti-AIDS drugs zidovudine and lamivudine. In fact, the above design uses polydimethylsiloxane (PDMS) or perfluorocarbons, while the proposed invention uses Nano-absorbent octa silica.

Solid phase micro extraction fiber structure and method of making

United States Patent 6759126

A solid phase micro extraction (SPME) fiber including a fiber and a deactivated surface-bonded sol-gel coating on a portion of the fiber to form a solid phase micro extraction coating on the portion of the fiber, wherein the solid-phase micro extraction coating is capable of preconcentrating trace organic compounds in various matrices. A sol-gel method of preparing SPME fibers with chemically bonded stationary phase coatings that serve as solvent-free extraction media including the step of chemically bonding the sol-gel stationary phase with the SPME fiber surface during its creation through sol-gel reactions.

In this invention, ODS nanoparticles with covalent bonding were used on the surface of a fiber (steel base) and by applying voltage, it was used for simultaneous measurement of anti-AIDS drugs zidovudine and lamivudine.

Methods of Preparation and Manufacture of Biocompatible Solid-Phase Micro Extraction Coatings and Coated Devices

United States Patent Application 20120228228

A process for manufacturing a fiber or other device with a biocompatible coating for using the fiber in solid phase micro extraction (SPME) of a small molecule of interest from a matrix. The process includes the step of coating the fiber/device with a coating of a biocompatible polymer and a solvent having solid phase micro extraction (SPME) particles with pores dimensioned to absorb the small molecule of interest from the matrix suspended therein. The process also includes the steps of drying the coated fiber/device to remove the solvent and curing the dried coated fiber at an elevated temperature.

BIOCOMPATIBLE SOLID-PHASE MICROEXTRACTION COATINGS AND METHODS FOR THEIR PREPARATION

United States Patent Application 20090026122

A biocompatible coating for solid phase micro extraction (SPME) of a small molecule from a biological matrix. The coating comprises SPME particles and a biocompatible polymer. The biocompatible polymer (e.g. polyacrylonitrile) reduces adsorption of proteins or macromolecules onto the SPME particles and allows the SPME particles to extract the small molecule from the matrix. A process for coating a flexible fiber with a biocompatible coating. The process comprises: coating the fiber with a suspension of SPME particles, the SPME particles being suspended in a solution of a biocompatible polymer and a solvent, the biocompatible polymer can comprise polyacrylonitrile (PAN); drying the coated fiber to remove the solvent; and curing the dried coated fiber at an elevated temperature.

In this invention, ODS nanoparticles with covalent bonding were used on the surface of a fiber (steel base) and by applying voltage, it was used for simultaneous measurement of anti-AIDS drugs zidovudine and lamivudine. In fact, the above design uses polyacrylonitrile (PAN), while the proposed invention uses Nano-absorbent octa silica.

Offline solid phase micro extraction sampling system

United States Patent 7464614

An offline solid phase micro extraction (SPME) sampling apparatus for enabling SPME samples to be taken a number of times from a previously collected fluid sample (e.g. sample atmosphere) stored in a fused silica lined bottle which keeps volatile organics in the fluid sample stable for weeks at a time. The offline SPME sampling apparatus has a hollow body surrounding a sampling chamber, with multiple ports through which a portion of a previously collected fluid sample may be (a) released into the sampling chamber, (b) SPME sampled to collect analytes for subsequent GC analysis, and (c) flushed/purged using a fluidically connected vacuum source and purging fluid source to prepare the sampling chamber for additional SPME samplings of the same original fluid sample, such as may have been collected in situ from a headspace.

SOLID-PHASE MICROEXTRACTION COATINGS AND METHODS FOR THEIR PREPARATION

United States Patent Application 20120164286

In this invention, ODS nanoparticles with covalent bonding were used on the surface of a fiber (steel base) and by applying voltage, it was used for simultaneous measurement of anti-AIDS drugs zidovudine and lamivudine. In fact, the proposed invention uses Nano-absorbent octa silica.

Nuclear drugs play an important role in antiviral therapy for the human immunodeficiency virus (HIV), the hepatitis B and C viruses, and the human herpes virus. Purification of the Matrix and Extraction of Nuclear Drugs The purpose of the sample matrix through in vivo pharmacokinetic studies has attracted much attention in biochemical research. Therefore, the need to develop fast, sensitive and simple methods for measuring these materials is undeniable. In this invention, Nano-ODS adsorbent was first synthesized and deposited on a stainless steel wire with covalent bonding by sol-gel method. The covalent bonding of the adsorbent and the substrate makes the adsorbent stronger in the DI-SPME method and eliminates the problems compared to many commercially made fibers. This fiber was then used in EE-DI-SPME-HPLC-UV method to extract and measure AIDS drugs. Detergent type and volume of sample pH, applied voltage, ionic strength, sample volume, sample rotation speed, extraction time and desorption time were optimized as parameters affecting the efficiency of the mentioned method. The results showed that this method has the ability to pre-concentrate and measure the target analytes in real samples.

The main part of solid phase micro-extraction method based on Fiber SPME is the coating of the fiber surface. Commercially available coatings include polyacrylate (PDMS) polydimethylsiloxane (PA), divinyl benzene polydimethylsiloxane (PDMS-DVB) and carbovax di vinyl benzene (CW-DVB). These fibers have important problems such as relatively low thermal stability (usually 200 to 270 degrees Celsius), instability and swelling in aqueous and organic solvents, brittleness, shedding of fiber coating and high cost. The reasons given are that handmade fibers with better properties are a good alternative to these fibers. In the manufacture of handmade fibers in recent years, attempts have been made to use nanomaterials as adsorbents. The type of adsorbent used in this method must be suitable for the desired analyte and can improve the sensitivity and accuracy of the method. On the other hand, solid phase micro extraction methods in cases where the analyte concentration is very low, the analyte is very polar or ionic, etc., have difficulty in detection. To enhance SPME methods, various techniques such as using voltage, cooling, using ultrasound, using vacuum have been used. The application of voltage can be used to amplify the methods mentioned in the measurement of ions or compounds that can be ionized. Accordingly, in this invention, for the first time, Nano-ODS octa-silica Nano sorbent was synthesized by a simple green sol-gel method and used as a micro sorbent for SPME fiber coating. This adsorbent was used for the simultaneous extraction and pre-concentration of anti-AIDS drugs zidovudine and lamivudine in biological fluids of the human body. Voltage-enhanced solid-phase micro extraction method by direct immersion EE-DI-SPME was used for sampling and pre-concentration and HPLC technique was used for measurement.

Solution of problem

A steel wire was chosen as the fiber support.

In order to prepare the wire surface and place the adsorbent on it, 2 cm of it was cut.

In order to wash it and remove contaminants as well as activating steel wire, it was washed with water and methanol.

Then it was rinsed in sulfuric acid solution for 5 minutes and then with soda solution and finally dried at room temperature.

In the second stage, the Nano-ODS adsorbent was deposited on the steel wire surface by sol-gel method with covalent bonding. By mixing 3.5 ml of TEOS as a precursor for sol, 2.5 ml of ammonia (catalyst), 4.5 ml of water and 50 ml of ethanol (solvent) and stir at a temperature of ℃ 60 for 90 minutes. Until the silica cell is formed as colloidal particles.

After this step, 2 ml of trichloroacetic decyl silane was added dropwise to the solution, and the solution was stirred at high speed for 19 h.

Then 2 cm of the activated steel wire was immersed in the previous step in the sol solution with the help of a fiber spinner at 100 rpm for two minutes.

Finally, the prepared fiber was placed in an oven at a temperature of 100 degrees for half an hour.

SEM device was used to investigate the structure of the adsorbent placed on the surface of steel wire and the composite specifications were confirmed. shows the SEM image of the composite.

To perform the extraction by EE-DI-SPME-HPLC-UV method, the sample solution containing the target drugs is poured into the extraction container and its lid is closed. Then, the fiber prepared from Nano-ODS adsorbent as a cathode and a platinum wire as an anode were connected to the DC voltage application device. After the extraction process, the adsorbed analytes were desorbed and identified by HPLC.

Advantage effects of invention

Applying voltage causes the transfer of the desired analyte to the fiber and the absorber to increase, thus increasing the speed and efficiency of the method.

Compared to ordinary fibers, the coating created is much more resistant to chemical and mechanical stresses and has a longer life. This is due to the chemical bond between the steel base and the adsorbent.

No need to use expensive materials (as a binder between the surface and the coating).

The adsorbent is synthesized at the nanoscale, which has a much higher surface-to-volume ratio than other adsorbents.

Its manufacturing process is simple and reproducible, and it is possible to commercialize the introduced method and the fiber prepared with the desired adsorbent.

The cost of construction and maintenance of the proposed system is cost-effective.

: SEM images related to Nano-ODS

: EDX Nano-ODS range

: Chromatogram of real sample

: SEM images related to Nano-ODS

: EDX Nano-ODS range

: Chromatogram of real sample

Examples

To ensure the correct operation of the proposed EE-DI-SPME-HPLC-UV method, it was used to analyze several sample samples and the results were compared with valid methods. For extraction by EE-DI-SPME-HPLC-UV method, 20 ml of standard solution containing 20 μg of each target analyte was poured into a small flask and placed on a heater. Then, fiber prepared from Nano-ODS adsorbent was connected to the power supply as a cathode and a platinum wire as an anode. After extraction, the fiber was separated from the power supply and washed with 200 μl of methanol for 5 minutes. Finally, 20 μl of methanol solution was injected into HPLC to measure the amount of analytes.

The fiber prepared with the introduced adsorbent has the ability to absorb the desired drugs. Applying voltage also increases the sensitivity and efficiency of the method as much as possible. The desired conditions were optimized for this measurement and the calibration diagram was drawn under the best conditions. Measurements were performed by high pressure liquid chromatography. A linear range of 0.05-5000 ng / ml with a greater correlation coefficient of 0.99 indicates the good performance of this method in measuring zidovudine and lamivudine. Samples of three pills were obtained from domestic pharmaceutical companies and were tested by EE-DI-SPME-HPLC-UV method and the amount of zidovudine and lamivudine in them was evaluated. The chromatogram of the real sample is shown in the figure.

The results of this project are widely used in the analysis of drug compounds and biological body fluids. It can be used as a rapid and one-step analysis in the pharmaceutical laboratory without the need for a time-consuming sample preparation step and without the need to use toxic and carcinogenic substances and solvents.

Claims

A new solid phase micro extraction fiber (SPME) was fabricated by covalent bonding of octa-decyl silica (Nano-ODS) nanoparticles on a stainless steel wire surface and Nano-adsorbent was deposited on a steel fiber surface by a simple green sol-gel method.
According to Claim 1, fiber prepared by solid phase micro extraction with direct voltage-amplified immersion (EE-DI-SPME) for used to the separation, extraction and pre-concentration of antidiabetic drugs zidovudine and lamivudine in biological fluids of the human body.
According to Claim 2, Nano sorbents and fibers were investigated by FT-IR, SEM and EDX techniques and its structure as well as the existence of a covalent bond between steel and Nano-ODS was confirmed.
According to Claim 3, the results of extraction of zidovudine and lamivudine from standard and real samples as well as evidence confirmed by FT-IR, SEM and EDX techniques showed that ODS nanoparticles have a high porosity and contact surface on the steel surface. Due to their suitable polarity and high strength, they can be used to measure zidovudine and lamivudine in biological fluids of the human body and in medical laboratories.