Nanocrystalline cellulose as a biotemplate for preparation of porous titania thin film as a sorbent for thin film microextraction of ketorolac, meloxicam, diclofenac and mefenamic acid

Highlights

• Cellulose nanocrystals were used as a green biotemplate to prepare tunable porosity.

• Porous titania thin film was obtained through bio-templating with NCC.

• The porous morphology can be tailored through variation in precursor composition.

• The porous film was applied to extract nonsteroidal anti-inflammatory drugs simultaneously.

• Porous titania thin film followed by HPLC-UV exhibited high performance for TFME.

Abstract

The present study included the procedure of preparing porous titania thin film using a direct nanocrystalline cellulose templating (NCC) as a bio-template. The microextraction applicability of the porous film was investigated by thin film microextraction (TFME) of the nonsteroidal anti-inflammatory drugs (NSAIDs) including ketorolac, meloxicam, diclofenac and mefenamic acid from different types of urine sample. The extracted NSAIDs were analyzed by HPLC-UV. Under optimum conditions, the calibration curves were linear within the range of 1.0–500 µg L⁻¹ (2.0–200 µg L⁻¹ for ketorolac, 2.0–500 µg L⁻¹ for meloxicam, 1.0–200 µg L⁻¹ for diclofenac and 1.0–200 µg L⁻¹ for mefenamic acid). The limit of detection was found to be between 0.2 and 0.5 µg L⁻¹. The calculated intra- and inter-day relative standard deviations RSDs% (n = 3) at concentration level of 10 µg L⁻¹ were less than 6.3% and 6.0%, respectively. Finally, the method was successfully applied to determine selected NSAIDs in urine samples from different human individuals.

Introduction

Sample preparation is a crucial step in most of the analytical methods. Depending on the extraction phase, sample preparation strategies are categorized into Solid-Phase Extraction (SPE) and Liquid-Phase Extraction (LPE). SPE is very popular among sample preparation methods. Conventional SPE is administered by passing a high volume of liquid sample through a sorbent bed to retain target analytes. Solid phase microextraction (SPME) and thin film microextraction (TFME) are two popular types of development in SPE both of which were introduced by Pawliszyn and co-workers [1], [2]. In comparison to SPME, both the volume and the surface-to-volume ratios of extraction phase are significantly enhanced in TFME.

Given their large surface to volume ratio and tunable pore size, nanoporous materials have gained significant attention in recent years. According to the International Union of Pure and Applied Chemistry (IUPAC), nanoporous materials are divided into three main categories including microporous (<2 nm), mesoporous (2–50 nm), and macropores (>50 nm). A wide range of nanoporous materials such as mesoporous metal oxides [3], mesoporous polymers [4] and metal-organic frameworks [5], [6] has been synthesized and used for gas separation, microextraction, adsorption, catalysis, etc. There have been many attempts to synthesize mesoporous materials with tailored meso-structure and uniform pore size distribution.

Template synthesis is a very effective approach that has widely been used in recent years. However, removal of the templates without attacking the substrate is usually a challenging step. Templates are usually divided into hard and soft groups. In a first successful attempt, a mesoporous material with tailored mesostructure and uniform pore size distribution was presented by Kresge and co-workers who used cetyltrimethylammonium bromide (CTAB) as a template [7]. The scientists then suggested the soft-templated self-assembly approach to synthesize mesostructures. In this scenario, the non-covalent forces form the spontaneous organization of materials without any external aid [8]. In another attempt, Moriguchi and co-workers presented a procedure based on using ionic surfactant templating to prepare carbon materials with periodic mesoporous structure [9]. Moreover, nonionic surfactants were also explored to form mesostructures [10]. Compared to ionic surfactants, nonionic surfactants have relatively low toxicity, and cost as well as better degradability. Although the soft templating improved the synthesis procedure of porous materials, depending on the precursor, the surfactant and the interaction between them limited the preparation of many mesoporous materials.

The other widely used strategy to create porous materials is hard templating method. This approach consists of three main steps including: (a) the preparation of the template and penetration of precursor to the unoccupied space of template, (b) using synthetic strategy such as precipitation, sol-gel or hydrothermal method to condense the precursor into an inter-connected framework and (c) removal of the template.

In the hard-templating method, the porosity of the product can be tuned by the structure of the templates. Templates are usually categorized into two major categories including synthetic materials (porous materials, surface active agents and nanoparticles) and natural substances (biological molecules, nanomineral, cells and tissues) [11], [12]. Removal of the template is an important step. The popular removal methods are dissolution, sintering and etching.

Silica and alumina are among the most frequently used hard templates, enabling shape persistent replication of various morphologies. However, removal of the solid inorganic templates without attacking the target material is usually challenging. In this respect, biomaterials are very attractive as shape persistent pore generators since they can provide a wide variety of shapes and sizes and generally they can be easily removed.

Cellulose is a linear homopolymer involving D-glucose. D-glucose is a relatively rigid molecule, which when polymerized gives cellulose its characteristic properties such as hydrophilicity and easy degradability. Cellulose contains both amorphous and crystalline areas.

Nanocellulose (NC) which is a cellulose with nano-scale dimensions in width, length or both is grouped into four different subcategories including: cellulose nanocrystals (NCC), cellulose nanofibrils (CNF), bacterial cellulose (BC) and spherical nanocellulose (SNC) [13]. NCC which is also called as cellulose whiskers, has drawn more attention from both researchers and academicians. NCC has a rod-like structure with about 90% crystallinity. Due to the outstanding features of cellulose-based resources such as being abundant, ease of template removal and renewable natural resources, the interests of scientist in using NCC as a template for synthesis of nanomaterial have increased [14], [15], [16]. Nowadays, NC has been used as a template for the growth of metal nanotubes, isolated metal nanoparticles and different metal oxides [17], [18]. In comparison to soft templates, NCC templating has some advantages including higher temperature stability and tunable dimensions.

Titanium dioxide (Titania), also known as titanium(IV) oxide is a material of high importance to be used as sorbent, catalyst, photocatalyst and semiconductor. The capability of titania-based devices is often related to the porosity of the deposited titania thin films [19].

We have presented a strategy to prepare porous titania thin film by biotemplating with NCC in the current study. The extracted NCC was used as a novel shape-persistent templating agent enabling the straightforward synthesis of mesoporous titania thin films. The NCC was used as a removable template. Moreover, a slow template removal can be used to achieve pore widening.

NCC was extracted from cotton linters via sulfuric acid hydrolysis. To the best of our knowledge, it is the first report regarding the microextraction application for the direct formation of cellulose-templated titania thin films on substrates. The presented one-pot synthesis provides mesoporous TiO₂ thin film with unique porosity, which can be used as a sorbent for TFME. In addition, the pore distribution, surface area and pore size of the NCC-templated titania sorbent can be tuned through further modification using the same template. In order to approve the extraction ability of the prepared porous film, the nonsteroidal anti-inflammatory drugs (NSAIDs) including Ketorolac, meloxicam, diclofenac and mefenamic acid were selected as the model compound and extracted through TFME using the prepared film as extraction device. The effective extraction factors were optimized with the aid of Box-Behnken design (BBD) and response surface methodology (RSM) after the first screening by Plackett–Burman design (PBD). Finally, the method was used to determine the selected NSAIDs in urine samples followed by HPLC-UV.