Microliquid/Liquid Interfacial Sensors: Biomimetic Investigation of Transmembrane Mechanisms and Real-Time Determinations of Clemastine, Cyproheptadine, Epinastine, Cetirizine, and Desloratadine.

Antihistamines relieve allergic symptoms by inhibiting the action of histamine. Further understanding of antihistamine transmembrane mechanisms and optimizing the selectivity and real-time monitoring capabilities of drug sensors is necessary. In this study, a micrometer liquid/liquid (L/L) interfacial sensor has served as a biomimetic membrane to investigate the mechanism of interfacial transfer of five antihistamines, i.e., clemastine (CLE), cyproheptadine (CYP), epinastine (EPI), desloratadine (DSL), and cetirizine (CET), and realize the real-time determinations. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques have been used to uncover the electrochemical transfer behavior of the five antihistamines at the L/L interface. Additionally, finite element simulations (FEMs) have been employed to reveal the thermodynamics and kinetics of the process. Visualization of antihistamine partitioning in two phases at different pH values can be realized by ion partition diagrams (IPDs). The IPDs also reveal the transfer mechanism at the L/L interface and provide effective lipophilicity at different pH values. Real-time determinations of these antihistamines have been achieved through potentiostatic chronoamperometry (I-t), exhibiting good selectivity with the addition of nine common organic or inorganic compounds in living organisms and revealing the potential for in vivo pharmacokinetics. Besides providing a satisfactory surrogate for studying the transmembrane mechanism of antihistamines, this work also sheds light on micro- and nano L/L interfacial sensors for in vivo analysis of pharmacokinetics at a single-cell or single-organelle level.

Simultaneous Determination of Montelukast Sodium and Loratadine by Eco-Friendly Densitometry and Spectrophotometric Methods.

Recently, the aim of analytical community is to reduce the usage of hazardous chemicals; so eco-friendly, rapid, selective and cost-effective methods were developed for simultaneous determination of montelukast sodium (MKT) and loratadine (LRT). The first method was based on chromatographic separation performed on precoated silica gel 60 GF254 plates with ethyl acetate-ethanol 9: 1 (v/v) as the mobile phase. The developed plates were scanned and quantified at 260 nm. The method gives linear correlation over concentration ranges of 0.3-3.6 µg/spot and 0.2-4.0 µg/spot for MKT and LRT, respectively. It was also successfully applied to analysis of both drugs in their pharmaceutical preparation and human plasma. The other methods are UV-spectrophotometric methods based on smart spectra manipulating to zero order spectrum of each drug. These methods are named response correlation (RC), a-centering and ratio derivative methods. RC and a-centering methods were dependent on the presence of an isosbestic point between the overlapped spectra of both drugs. While ratio derivative method based on manipulation of the ratio spectra of both drugs. The two drugs obey Beer-Lambert law over the concentration ranges of 3.0-30.0 µg/mL in the three spectrophotometric methods. Moreover, the greenness of the developed methods is assessed using suitable analytical Eco-Scale and Green Analytical Procedure Index.

Rapid and sensitive method for simultaneous determination of citalopram with antihistamines by liquid chromatography.

A highly sensitive liquid chromatographic method with UV detection has been developed for simultaneous determination of citalopram, levocetirizine and loratadine in bulk drug, pharmaceutical formulation and human serum at 230nm employing 80:20 v/v methanol-water as mobile phase with pH3.5, adjusting flow rate of 1.0mL.min-1. Separation was achieved on Shimadzu Shim-pack CLC-ODS (M) 25M column within the linear range of 0.4-12.5, 0.8-25 and 0.8-25µg.mL-1 with R2 >0.998 and detection limit 7.75, 3.35 and 10.26ng.mL-1respectively. ICH guidelines were followed for validation showing 0.22-1.76, 0.06-1.83 and 0.22-2.11% RSD. The recovery of analytes in tablets and serum was found to be in acceptable range. The method was fruitfully employed for the determination of studied analyte in pharmaceutical formulation and human serum.

A multivariate quantification of Box-Behnken design assisted method development and validation of dextromethorphan hydrobromide and desloratadine simultaneously by reverse-phase HPLC in in-house syrup formulation.

An innovative high-performance liquid chromatography assay method was developed and validated for quantification of dextromethorphan hydrobromide and desloratadine simultaneously in monophasic liquid formulation by preparing syrup containing 30 mg/5 mL of dextromethorphan hydrobromide and 1.2 mg/mL of desloratadine. The chromatographic severance was executed by gradient solution A and B. The composition of buffer solution A contained 0.05 M monobasic potassium, then 1 mL triethylamine was added to it and the pH was adjusted to 2.3 with orthophosphoric acid. Methanol was used as solution B. The gradient elution was executed with Kromasil C8 (250 mm × 4.6 mm) column having 1.5 mL/min flow rate and 20 µL injection volume with UV-estimation at 254 nm for dextromethorphan hydrobromide and DES. The present research was planned according to Box-Behnken design by utilizing design expert software, using four factors such as column temperature (A), flow rate (B), mobile phase-organic phase (C), and pH (D); correspondingly the selected response variables were resolution between A and B, that is, desloratadine and methyl paraben (Y1), tailing of dextromethorphan hydrobromide (Y2), and tailing of desloratadine (Y3). The parameters such as system suitability, linearity, accuracy, precision, robustness, limit of detection, limit of quantitation, and ruggedness were analyzed to validate the developed method in accordance with current regulatory guidelines.

Carboxymethyl-botryosphaeran stabilized carbon nanotubes aqueous dispersion: A new platform design for electrochemical sensing of desloratadine.

The polysaccharide carboxymethyl-botryosphaeran (CMB) was used to improve the dispersion of multi-walled carbon nanotubes (MWCNTs) in water. This feature was applied in modifying a glassy carbon electrode (GCE) to construct a sensitive voltammetric sensor for the determination of desloratadine (DESL), a tricyclic antihistamine. The morphology and spectroscopic behavior of the sensor were evaluated. The modified sensor was characterized as homogeneous, and presented a higher electroactive area and a lower charge transfer resistance compared to the unmodified GCE. Using linear sweep voltammetry at 25 mV s-1, the developed sensor presented a sensitivity of 1.018 µA L µmol-1 in the linear working range of 1.99-32.9 µmol L-1, with a detection limit of 0.88 µmol L-1 of DESL in 0.10 mol L-1 potassium hydrogen-phosphate solution (pH 8.0). In addition, the sensor showed excellent repeatability with a relative standard deviation of only 1.02% for a sequence of 10 measurements. The sensor was successfully applied in the analysis of pharmaceutical preparations containing DESL, with equivalent results compared to a validated spectrophotometric method at the 95% confidence level. The sensor was also employed in the analysis of a spiked sample of DESL in rat serum.

Development of novel electrochemical sensor on the base of molecular imprinted polymer decorated on SiC nanoparticles modified glassy carbon electrode for selective determination of loratadine.

A novel and selective electrochemical sensor was successfully developed for the determination of loratadine by drop coating of synthesized loratadine molecularly imprinted polymers on the surface of glassy carbon electrode modified with silicon carbide nanoparticles. The performance of the constructed sensor was evaluated by cyclic voltammetry, scanning electron microscopy, and electrochemical impedance spectroscopy techniques. Under optimized conditions, the resulting calibration curve exhibited a linear response within a concentration range of 1-33µM with a low detection limit (S/N=3) of 0.15µM. Finally, the proposed method was successfully applied as a selective, stabile, sensitive, simple, reproducibility electrochemical sensor with good repeatability for the determination of loratadine in real samples and satisfactory results were obtained.

HPTLC Method for the Determination of Paracetamol, Pseudoephedrine and Loratidine in Tablets and Human Plasma.

A sensitive, accurate and selective high performance thin layer chromatography (HPTLC) method was developed and validated for the simultaneous determination of paracetamol (PAR), its toxic impurity 4-aminophenol (4-AP), pseudoephedrine HCl (PSH) and loratidine (LOR). The proposed chromatographic method has been developed using HPTLC aluminum plates precoated with silica gel 60 F254 using acetone-hexane-ammonia (4:5:0.1, by volume) as a developing system followed by densitometric measurement at 254 nm for PAR, 4-AP and LOR, while PSH was scanned at 208 nm. System suitability testing parameters were calculated to ascertain the quality performance of the developed chromatographic method. The method was validated with respect to USP guidelines regarding accuracy, precision and specificity. The method was successfully applied for the determination of PAR, PSH and LOR in ATSHI(®) tablets. The three drugs were also determined in plasma by applying the proposed method in the ranges of 0.5-6 µg/band, 1.6-12 µg/band and 0.4-2 µg/band for PAR, PSH and LOR, respectively. The results obtained by the proposed method were compared with those obtained by a reported HPLC method, and there was no significance difference between both methods regarding accuracy and precision.

Simultaneous determination of desloratadine and montelukast sodium using second-derivative synchronous fluorescence spectrometry enhanced by an organized medium with applications to tablets and human plasma.

A rapid, simple, and sensitive second-derivative synchronous fluorimetric method has been developed and validated for the simultaneous analysis of a binary mixture of desloratadine (DSL) and montelukast sodium (MKT) in their co-formulated tablets. The method is based on measurement of the synchronous fluorescence intensities of the two drugs in McIlvaine's buffer, pH 2.3, in the presence of carboxy methyl cellulose sodium (CMC) as a fluorescence enhancer at a constant wavelength difference (Δλ) of 160 nm. The presence of CMC enhanced the synchronous fluorescence intensity of DSL by 216% and that of MKT by 28%. A linear dependence of the concentration on the amplitude of the second derivative synchronous fluorescence spectra was achieved over the ranges of 0.10-2.00 and 0.20-2.00 µg/mL with limits of detection of 0.02 and 0.03, and limits of quantification of 0.05 and 0.10 µg/mL for DSL and MKT, respectively. The proposed method was successfully applied for the determination of the studied compounds in laboratory-prepared mixtures and tablets. The results were in good agreement with those obtained with the comparison method. The high sensitivity attained by the proposed method allowed the determination of MKT in spiked human plasma with average % recovery of 100.11 ± 2.44 (n = 3).

Validated selective spectrophotometric methods for the kinetic determination of desloratidine in tablets and in the presence of its parent drug.

Two novel selective validated methods have been developed for analysis of desloratidine (DSL) in its tablets formulation. Both were kinetic spectrophotometric methods, depend on the interaction of the secondary amino group in DSL with acetaldehyde to give N-vinylpiperidyl product. The formed N-vinylpiperidyl compound was reacted with 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil) to form colored N-vinylpiperidyl-substituted benzoquinone derivatives. The formed blue-colored derivative was measured at 672 nm. The reaction conditions were carefully studied and all factors were optimized. The molar ratio between the reactants was estimated and a suggested reaction mechanism was presented. The analysis was carried out using initial rate and fixed time (at 6 min) methods. The linear concentration ranges were 3-50 and 10 - 60 µg mL-1 with limits of detection of 3.2 and 2.2 µg mL-1 for the initial rate and fixed time methods, respectively. ICH guidelines were applied for analytical performance validation of the proposed methods. The presence of common excipients in the pharmaceutical formulation did not produce any significant interference, as well as from loratadine, which is the parent compound of DSL. Different commercially available tablets formulations containing were successfully analyzed, with, the percentage recovery ranging from 97.28-100.90 ± 0.7 2-1.41%. The obtained results were compared statistically with the reported method results. The proposed methods have similar accuracy and precision as the reported as indicated from the F- and t-test data.

Ultrafast high-resolution mass spectrometric finger pore imaging in latent finger prints.

Latent finger prints (LFPs) are deposits of sweat components in ridge and groove patterns, left after human fingers contact with a surface. Being important targets in biometry and forensic investigations they contain more information than topological patterns. With laser desorption mass spectrometry imaging (LD-MSI) we record 'three-dimensional' finger prints with additional chemical information as the third dimension. Here we show the potential of fast finger pore imaging (FPI) in latent finger prints employing LD-MSI without a classical matrix in a high- spatial resolution mode. Thin films of gold rapidly sputtered on top of the sample are used for desorption. FPI employing an optical image for rapid spatial orientation and guiding of the desorption laser enables the rapid analysis of individual finger pores, and the chemical composition of their excretions. With this approach we rapidly detect metabolites, drugs, and characteristic excretions from the inside of the human organism by a minimally-invasive strategy, and distinguish them from chemicals in contact with fingers without any labeling. The fast finger pore imaging, analysis, and screening approach opens the door for a vast number of novel applications in such different fields as forensics, doping and medication control, therapy, as well as rapid profiling of individuals.

Plasma-based ambient sampling/ionization/transmission integrated source for mass spectrometry.

Better sensitivity and interface of ambient sampling/ionization mass spectrometry remain a challenge. Herein, a novel, plasma-based, ambient sampling/ionization/transmission (PASIT) integrated source in a pin-to-funnel configuration was developed for the sensitive analysis of complex samples. With the funnel sleeve directly affected by direct-current discharge plasma, PASIT combines the ability to sample/ionize analyte molecules and then efficiently collect/transport charged mass species under atmospheric pressure and consequently shows an improved sensitivity. The integrated source enhances the signal intensity by more than 2 orders of magnitude compared with the previous pin-to-plate plasma source without significant background addition. A surface limit of detection (LOD) of 130 fmol mm-(2) (S/N = 3) has been achieved for clenbuterol on filter paper with an argon carrier gas. Demonstrated applications include the direct determination of active ingredients from drugs and symbolic compounds from natural plants and cholesterol from mouse brain tissue sections.

Processes involved in sweeping as sample enrichment method in cyclodextrin-modified micellar electrokinetic chromatography of hydrophobic basic analytes.

Sweeping is an enrichment method in MEKC, which includes following steps: stacking/destacking of the micelles, sweeping of analyte by the stacked/destacked micelles, destacking/stacking of the swept analyte zone and additional focusing/defocusing due to the retention factor gradient effect (RFGE). In this study, we investigate additional processes, regarding online focusing in cyclodextrin-modified MEKC (CD-MEKC) of hydrophobic basic analytes: dynamic pH junction (sample with pH different from that of BGE) and adsorption of analyte onto the capillary wall within the sample zone. It is demonstrated that the developed method for the assessment of the sweeping efficiency is also applicable to CD-MEKC taking ethylparaben as an example of acidic analytes and desloratadine as an example of basic analytes using different types of ß-cyclodextrin. Our previous results regarding RFGE as an additional focusing/defocusing effect in sweeping-MEKC are confirmed for the case that the apparent distribution coefficient differs for the sample and the BGE due to a different content of the complex-forming agent cyclodextrin and due to a pH difference between the sample and the BGE. Despite being significantly more hydrophobic than ethylparaben, desloratadine shows an unexpectedly low enrichment factor. This enrichment factor is nearly unaffected by the addition of CD to the BGE. This unexpected behavior is attributed to wall adsorption of the protonated hydrophobic basic analyte within the sample zone, which significantly counteracts the sweeping process. This assumption is corroborated by an improvement in the enrichment factor achieved via addition of a dynamic coating agent (triethylamine) to the sample solution.

Thin layer chromatography-densitometric determination of some non-sedating antihistamines in combination with pseudoephedrine or acetaminophen in synthetic mixtures and in pharmaceutical formulations.

The combination of certain non-sedating antihistamines (NSA) such as fexofenadine (FXD), ketotifen (KET) and loratadine (LOR) with pseudoephedrine (PSE) or acetaminophen (ACE) is widely used in the treatment of allergic rhinitis, conjunctivitis and chronic urticaria. A rapid, simple, selective and precise densitometric method was developed and validated for simultaneous estimation of six synthetic binary mixtures and their pharmaceutical dosage forms. The method employed thin layer chromatography aluminum plates precoated with silica gel G 60 F254 as the stationary phase. The mobile phases chosen for development gave compact bands for the mixtures FXD-PSE (I), KET-PSE (II), LOR-PSE (III), FXD-ACE (IV), KET-ACE (V) and LOR-ACE (VI) [Retardation factor (Rf ) values were (0.20, 0.32), (0.69, 0.34), (0.79, 0.13), (0.36, 0.70), (0.51, 0.30) and (0.76, 0.26), respectively]. Spectrodensitometric scanning integration was performed at 217, 218, 218, 233, 272 and 251 nm for the mixtures I-VI, respectively. The linear regression data for the calibration plots showed an excellent linear relationship. The method was validated for precision, accuracy, robustness and recovery. Limits of detection and quantitation were calculated. Statistical analysis proved that the method is reproducible and selective for the simultaneous estimation of these binary mixtures.

Utility of 4-chloro-7-nitrobenzofurazan (NBD-CI) for the Spectrophotometric and spectrofluorometric determination of several antihistamine and antihypertensive drugs.

New, sensitive, and selective spectrophotometric and spectrofluorometric methods have been developed for determination of clemastine hydrogen fumarate (Clem), loratadine (Lor), losartan potassium (Los), and ramipril (Ram) in both pure form and pharmaceutical formulations using 4-chloro-7-nitrobenzofurazan (NBD-CI), which is a highly sensitive chromogenic and fluorogenic reagent. The relation between absorbance at 470, 467, 471, and 469 nm and the concentration was linear over the ranges 5-35, 10-100, 10-90, and 10-120 microg/mL for Clem, Lor, Los, and Ram, respectively. The complexation products were also measured spectrofluorometrically at the emission wavelength 535 nm for Clem, Lor, and Ram and at 538 nm for Los with excitation at 477 and 452 nm for Clem and Lor, respectively, and 460 nm for both Los and Ram. The fluorescence intensity was directly proportional to the drug concentration over the ranges 0.05-0.5, 5-20, 1-6, and 2-15 microg/mL for Clem, Lor, Los, and Ram, respectively. The methods were successfully applied for the determination of the studied drugs in pharmaceutical dosage forms with excellent recovery.

Identification and determination of selected histamine antagonists by densitometric method.

The conditions for identification were determined for four histamine antagonists: clemastine fumarate, loratadine, cetirizine dihydrochloride and desloratadine by TLC (thin-layer chromatography) method. The selected chromatographic conditions were used to develop a densitometric method for the content determination of the histamine antagonists in medicinal products and substances. The statistical data showed adequate accuracy and precision of the developed methods.

Methodology for the validation of analytical methods involved in uniformity of dosage units tests.

Validation of analytical methods is required prior to their routine use. In addition, the current implementation of the Quality by Design (QbD) framework in the pharmaceutical industries aims at improving the quality of the end products starting from its early design stage. However, no regulatory guideline or none of the published methodologies to assess method validation propose decision methodologies that effectively take into account the final purpose of developed analytical methods. In this work a solution is proposed for the specific case of validating analytical methods involved in the assessment of the content uniformity or uniformity of dosage units of a batch of pharmaceutical drug products as proposed in the European or US pharmacopoeias. This methodology uses statistical tolerance intervals as decision tools. Moreover it adequately defines the Analytical Target Profile of analytical methods in order to obtain analytical methods that allow to make correct decisions about Content uniformity or uniformity of dosage units with high probability. The applicability of the proposed methodology is further illustrated using an HPLC-UV assay as well as a near infra-red spectrophotometric method.

Avaliação da fotoestabilidade de acetazolamida e loratadina e da capacidade de fotoproteção de seus complexos com ciclodextrinas / Assessing the photostability of acetazolamide and loratadine and the photoprotection capacity of its complexes with cyclodextrins

A fotoestabilidade é uma propriedade das moléculas que, quando utilizada como parâmetro farmacêutico, descreve como um fármaco responde à exposição à luz (solar ou artificial). No presente trabalho, foi avaliada a fotoestabilidade dos fármacos loratadina (LORA) e acetazolamida (ACZ) e de complexos LORA-ciclodextrinas. O estudo de fotoestabilidade de LORA (Capítulo 2) indicou que o fármaco é estável quando no estado sólido, porém, ocorre surgimento de coloração intensa. Por outro lado, quando em solução, observou-se degradação do fármaco, com surgimento de vários fotoprodutos denominados F1 a F15, dentre os quais foi possível identificar cinco compostos: F4 (C13H10N), F10 (C14H10CIN), F8 (C20H18CIN2O), F9 (C19H18CIN2) e F14 (C17H14CIN). A validação do método analítico CLAE, utilizado para quantificação de LORA em especialidades farmacêuticas (comprimidos e xaropes) é descrita no Capítulo 3. Na avaliação da fotodegradação forçada de formulações líquidas contendo LORA, foram degradados até 50% do fármaco. As formulações sólidas apresentaram-se fotoestáveis, observando-se perda de menos de 5% do fármaco. Não foram encontrados produtos de fotodegradação nas formulações, quando analisadas tal qual, obtidas do mercado. Dessa forma, as embalagens primárias garantiram sua estabilidade. A complexação de LORA com ciclodextrinas (Capítulo 4) mostrou-se um recurso bastante interessante para melhorar a fotoestabilidade do fármaco, uma vez que, após 12 horas de irradiação luminosa, é possível recuperar até 99% deste, quando na forma de complexo com γ-CD na proporção 1:1. Finalmente, o Capítulo 5 traz o método CLAE desenvolvido e validado para avaliação da acetazolamida (ACZ), o qual mostrou-se adequado para a quantificação do fármaco, obtendo-se ótima linearidade, precisão, exatidão e seletividade. Segundo as condições do guia Q1B, a ACZ se manteve estável quando submetida à radiação luminosa utilizando meios aquosos e no estado sólido. No entanto, a fotoestabilidade da ACZ foi afetada na presença de metanol, sendo possível quantificar três impurezas

Photostability is a property of molecules that, when used as a pharmaceutical parameter, can describe how a drug responds to exposure to light (either solar or artificial). In this study, the photostability of the drugs loratadine (LORA) and acetazolamide (ACZ), as well as LORA-cyclodextrin complexes, was evaluated. A study of the photostability of LORA (Chapter 2) indicated that the drug is stable in its solid form, however intense coloring does occur. On the other hand, when in solution form, degradation of the drug was observed, with the appearance of several photoproducts that we labled F1 to F15, among which it was possible to identify five compounds: F4 (C13H10N), F10 (C14H10CIN), F8 (C20H18CIN2O), F9 (C19H18CIN2) and F14 (C17H14CIN). The validation of the analytical method by HPLC, used for the quantification of LORA in pharmaceutical products (tablets and syrups) is detailed in Chapter 3. In the evaluation of forced photodegradation of liquid formulations containing LORA, up to 50% of the drug was degraded. The solid formulations proved to be photostable, with a loss of less than 5% of the drug. No photodegradation products were found in the formulations when they were analyzed "as is" (the way they were obtained from the commercial market). Accordingly, their primary packaging protected their stability. The complexation of LORA with cyclodextrins (Chapter 4) proved to be an effective resource for improving the photostability of the drug, since, after 12 hours of luminous radiation, it was possible to recover up to 99% of the drug, when in the complex form with γ-CD, in the proportion 1:1. Finally, Chapter 5 describes the HPLC method developed and validated for the evaluation of acetazolamide (ACZ), which proved to be adequate for the quantification of the drug, with the attainment of optimal linearity, precision, exactness and selectivity. According to the conditions of the Q1B guideline, ACZ was stable when subjected to luminous radiation using aqueous means and in its solid state. However, the photostability of ACZ was affected by the presence of methanol, and we were able to quantify three impurities

Stability-indicating micelle-enhanced spectrofluorimetric method for determination of loratadine and desloratadine in dosage forms.

A highly sensitive and simple spectrofluorimetric method was developed for the determination of loratadine (LRT) and desloratadine (DSL) in their pharmaceutical formulations. The proposed method is based on investigation of the fluorescence spectral behaviour of LRT and DSL in a sodium dodecyl sulphate (SDS) micellar system. In aqueous solution of acetate buffer of pH 4.5, the fluorescence intensities of both LRT and DSL were greatly enhanced (240%) in the presence of SDS. The fluorescence intensity was measured at 438 nm after excitation at 290 nm for both drugs. The fluorescence-concentration plots were rectilinear over the range 0.05-2.0 µg/mL for both LRT and DSL, with lower detection limits of 5.13 × 10(-3) and 6.35 × 10(-3) µg/mL for LRT and DSL, respectively. The method was successfully applied to the analysis of the two drugs in their commercial tablets, capsules and syrups, and the results were in good agreement with those obtained with the official or comparison methods. The proposed method is specific for the determination of LRT in the presence of other co-formulated drugs, such as pseudoephedrine. The application of the proposed method was extended to stability studies of LRT and DSL after exposure to different forced degradation conditions, such as acidic, alkaline and oxidative conditions, according to ICH guidelines.

Spray desorption collection: an alternative to swabbing for pharmaceutical cleaning validation.

Spray Desorption Collection (SDC) allows for much larger areas of surfaces to be sampled compared to traditional swabbing techniques, providing a valuable pre-concentration advantage. Closely related to desorption electrospray ionization (DESI), analytes from the sample surface are collected onto a selected collection surface, which in a second step can be analyzed directly. Here we demonstrate the application of SDC as a large surface area sampling tool coupled with paper spray MS (PS-MS) and demonstrate its capabilities for cleaning validation of pharmaceutical equipment for both acidic and basic active ingredients from an aluminium surface.

Development and validation of a novel stability-indicating reversed-phase high-performance liquid chromatography method for assay of loratadine and determination of its related compounds.

Loratadine is an important active pharmaceutical ingredient used in a wide variety of prescription and over-the-counter products for the treatment and relief of allergy symptoms. A novel stability-indicating gradient ion-pair RP-HPLC method for assay of loratadine and determination of both of its degradation compounds and process impurities has been developed. This method can separate loratadine from its eight structurally related compounds; it can also separate all of the related compounds from each other in less than 20 min. The stability-indicating capability of this method has been demonstrated by analyzing aged stability samples of loratadine. A 15 cm x 4.6 mm id YMC-Pack Pro C18 HPLC column was the primary column and a 15 cm x 4.6 mm id SunFire C18 column has been identified as an alternate (truly equivalent) column for this method. This gradient method uses mobile phases consisting of acetonitrile and an aqueous solution of 10 mM sodium acetate and 5 mM sodium dodecyl sulfate at pH 5.5. The new HPLC method was validated according to International Conference on Harmonization guidelines and proved to be suitable for routine QC use.