Local tolerance of intraarticular administration of lornoxicam into the rabbit knee joint.

The local tolerability of lornoxicam (Xefo) after single and repeated intraarticular administration was assessed in the rabbit and compared to established standard therapies (hyaluronic acid--Synvisc and the glucocorticoid triamcinolone--Triam), and the results are discussed in the context of the literature. Two local tolerance studies were performed using five male rabbits per group. Lornoxicam and competitor products were administered into the right knee joint in a volume of 500 µL. The contralateral left knee joint of the same animal was used as the control and was injected with water for injection. Three out of five animals were killed 72 h after the last administration, whereas the remaining two animals were subjected to a 2- or 6-week recovery period in the first and the second study, respectively. Findings revealed adaptive changes related to the mechanical irritation of the injection and to adaptive responses of the synoviocytes, but no signs of toxicity to bone or chondrotoxicity. Toxicokinetic analysis showed a fast and almost complete absorption of lornoxicam from the joints into the systemic circulation. As a conclusion, repeated intraarticular administration of lornoxicam was well tolerated in rabbits.

Effect of pentoxifylline and 5-fluorouracil/triamcinolone on laryngotracheal stenosis developing as a complication of tracheostomy: study in rats.

We aimed to investigate the prophylactic effect of pentoxifylline (PTX) and 5-fluorouracil (5-FU) on laryngotracheal stenosis in tracheotomised rats by evaluating blood glutathione peroxidase (GPx) and superoxide dismutase activities and by histopathological evaluation of laryngotracheal segment. Randomized prospective single-blind study. Standard vertical tracheotomy was performed on 24 rats. Then, the animals were randomly divided into three groups. Intraperitoneal PTX administered to group A (study group) for 10 days. 5-FU was injected in paratracheal tissues in group B (study group) for 10 days. In group C (control group), intraperitoneal saline was administered for 10 days. After 10 days, tracheal cannules were removed. For biochemical analysis, two blood samples were obtained. Three weeks later, all animals were euthanized and trachea specimens were harvested. Stenosis index and mean wall thickness in PTX group were lower as compared to other groups but the difference was statistically insignificant. Minimum inflammation and fibrosis plus maximum epithelial regeneration were seen in PTX group. In addition, GPx activity was at highest level in PTX group and a statistically significant difference was found between control and PTX groups (P = 0.024) though the difference between remaining groups was statistically insignificant (P = 0.121). Superoxide dismutase activity was highest in PTX group but no statistically significant difference was found between the three groups (P = 0.305). The administration of PTX increases GPx activity and it may have some effect on tracheal scar formation which develops following tracheostomy.

Effects of pimecrolimus versus triamcinolone on Langerhans cells after UV exposure.

BACKGROUND/PURPOSE: Pimecrolimus is a topical immunomodulator for atopic dermatitis. Concerns regarding malignancy risk resulted in its black box warning in 2006. The purpose of this study is to determine the effects of pimecrolimus on Langerhans cells (LC), mediators of the cutaneous immunity UV-irradiated skin. METHODS: A RCT was conducted investigating pimecrolimus 1% cream vs triamcinolone 0.1% cream on UV-irradiated epidermal LC on 20 healthy volunteers. Punch biopsies were stained with antibodies to CD1a, HLADR and CD83. RESULTS: Triamcinolone caused more depletion in UV-irradiated CD1a(+) epidermis relative to pimecrolimus treatment. (P=0.030). Using HLA-DR as a pan-marker for APCs, pimecrolimus caused marginally less depletion than triamcinolone (P=0.013). Using anti-CD83 as a maturation marker, UV-irradiated skin treated with pimecrolimus showed more mature LC than skin treated with triamcinolone (P=0.00090). CONCLUSION: UV-induced changes in LC are minimally affected by pimecrolimus, compared with triamcinolone.

Chitosan coated liposomes (CCL) containing triamcinolone acetonide for sustained delivery: A potential topical treatment for posterior segment diseases.

Drug delivery to the posterior eye is limited by epithelial and mucosal barriers limiting the topical administration of drugs leading to invasive modes of repeated long-term painful administration of drugs. Several constructs of liposomes have been prepared to counter this challenge yet are often limited by size and surface charge resulting in poor encapsulation efficiency, low retention time, and poor permeability. In the present study, chitosan coated liposomes (CCL) were prepared to address these challenges. Conventional liposomes encapsulating Triamcinolone Acetonide (TA) were compared with their chitosan coated counterpart for drug loading and release studies. CCL showed a higher encapsulation efficiency (74%), and a highly positive surface charge (+41.1Mv), increased retention time and sustained release. Choroidal neovascularization (CNV) rat models were generated to assess the efficiency of CCLs as nanocarriers in drug delivery. Significant amount of TA was found to be present and retaining in the eye after fifteen days of treatment with CCL, as shown by HPLC analysis. The results showed successful penetration of the construct via corneal mucosal barrier and its accumulation in vitreous body. The analysis shows that this chitosan based liposomal construct can be employed as a potential topical delivery system for treating posterior segment diseases.

Elastic net of polyurethane strands for sustained delivery of triamcinolone around silicone implants of various sizes.

We propose an elastic net made of a biocompatible polymer to wrap silicone implants of various sizes, which also allows for the sustained release of an anti-inflammatory drug, triamcinolone, to prevent fibrosis. For this, we first prepared a strand composed of a mixture of polyurethane and triamcinolone via electrospinning, which was then assembled to prepare the elastic drug-delivery net (DDN). The DDN was prepared to just fit for wrapping the small silicone implant sample herein, but was also able to wrap a sample 7 times as large at 72% strain due to the elastic property of polyurethane. The DDN exhibited sustained drug release for 4 weeks, the profile of which was not very different between the intact and strained DDNs. When implanted in a subcutaneous pocket in living rats, the DDN-wrapped silicone implant samples showed an obvious antifibrotic effect due to the sustained release of triamcinolone. Importantly, this effect was similar for the small and large silicone samples, both wrapped with the same DDN. Therefore, we conclude that this drug-loaded net made of an elastic, biocompatible polymer has high potential for sustained drug delivery around silicone implants manufactured in various sizes.

Supramolecular aggregates of cyclodextrins with co-solvent modulate drug dispersion and release behavior of poorly soluble corticosteroid from chitosan membranes.

In this study, the ability of different beta-cyclodextrins to facilitate homogeneous dispersion of triamcinolone acetonide (TA) into chitosan membranes is assessed. Drug loading was assessed through atomic force microscopy (AFM), scanning electron microscopy (MEV-FEG), and X-ray diffraction analyses. Drug interactions with the co-polymer were investigated with Fourier transform infrared spectroscopy, thermal analyses. Swelling assay, and in vitro drug release experiment were used to assess TA release behavior. Undispersed particles of drug were observed to remain in the simple chitosan membranes. Hydroxypropyl-ß-cyclodextrin enabled the dispersion of TA into chitosan membranes and subsequent sustained drug release. In addition, the membrane performance as a drug delivery device is improved by adding specified amounts of the co-solvent triethanolamine. The experimental data presented in this study confirm the utility of our novel and alternative approach for obtaining a promising device for slow and controlled release of glucocorticoids, such as triamcinolone acetonide, for topical ulcerations.

Systemic safety of serial intralesional steroid injection for subglottic stenosis.

OBJECTIVES/HYPOTHESIS: Serial intralesional steroid injection (SILSI) has recently been proposed as an effective scar-modifying therapy for subglottic stenosis (SGS). We aimed to explore the systemic absorption of steroid following SILSI and to characterize the magnitude and chronicity of any effect observed. Specifically, we aimed to show that any effect resolves prior to the next intralesional injection. STUDY DESIGN: Prospective, observational pilot study. METHODS: Patients were injected intralesionally with 40 to 200 mg triamcinolone. Serum cortisol, as well as white cell counts and inflammatory markers were measured at day 0 (baseline), 1, 7, and 28. Salivary cortisol was measured at baseline and for 7 consecutive days following injection. RESULTS: Six patients with idiopathic SGS were recruited. At baseline, serum cortisol measured 284.0 ± 61.4 nmol/L and fell significantly to 15.5 ± 4.3 nmol/L 1 day following triamcinolone injection (P = .03). At day 7, serum steroid levels showed significant recovery to 221.8 ± 78.9 nmol/L (P = .03) and further rose to 279.5 ± 29.9 nmol/L at 28 days (P = .07). Salivary cortisol exhibited a similar pattern with significant recovery by day 6 (P = .04) and suggestion of exponential clearance of triamcinolone systemically. White cell counts were also affected by systemic absorption of exogenous steroid. No significant change in inflammatory markers was observed. CONCLUSIONS: Our findings demonstrate systemic absorption of steroid following SILSI, with acute hypothalamic-pituitary-adrenal (HPA) axis suppression. However, normalization of HPA axis function by day 7 suggests that although acute steroid side effects should be discussed with patients, no cumulative systemic steroid side effect would occur with serial injections. LEVEL OF EVIDENCE: 2 Laryngoscope, 129:1634-1639, 2019.

Investigation into the mechanism by which cyclodextrins influence transdermal drug delivery.

The objective of this study was to investigate the mechanism by which hydroxypropyl-beta-cyclodextrin (HPCD) increases transdermal permeation. Hairless mouse skin was pretreated with HPCD solutions for up to 4 h. After removing the HPCD, corticosteroid-containing suspensions were applied and the transdermal flux and skin accumulation of two model drugs were investigated. After pretreatment, changes to the stratum corneum endothermic melting transitions were determined as an indication of HPCD-induced lipid disorganization. Results demonstrated that HPCD pretreatment had no significant effect on the transdermal permeation or skin accumulation of the model corticosteroids. These findings suggest that HPCD functions to enhance the apparent solubility of the drug in the formulation, thus increasing transdermal permeation rather than extracting lipids from the skin.

[Optic atrophy subsequent to epiretinal triamcinolone deposits in an eye following inner limiting membrane peeling]. / Optikusatrophie nach epiretinalen Triamcinolon-Ablagerungen in einem Auge mit entfernter Membrana limitans interna.

BACKGROUND: Although current in vitro studies show local cytotoxicity of triamcinolone (TA) crystals if they are in direct contact with cells, a toxic effect of epiretinal TA deposits has not been reported yet clinically. For the first time, we present a case of potential cytotoxicity of epiretinal TA deposits in vivo. CASE REPORT: A 68-year old patient underwent a re-vitrectomy with peeling of a macular pucker and the internal limiting membrane (ILM) combined with an intravitreal injection of 25 mg TA due to a secondary macular pucker with cystoid macular edema. Postoperatively, pronounced epiretinal deposits of TA crystals were identified in the area of the posterior pole. Two months after the injection a consecutive optic atrophy with central visual field defect and severe reduction of the visual acuity to hand movements was apparent. CONCLUSION: Our case report indicates possible in-vivo toxicity of TA deposits in eyes subsequent to vitrectomy and peeling of the ILM. This is in accordance with previous in-vitro studies showing ILM and vitreous to be protective biological factors, but demonstrate pronounced cytotoxicity if TA crystals are allowed to directly adhering to denuded ganglion cells. Hence, we consider that TA injection should be carefully weighed in those patients with prior ILM removal.

Hyaluronic Acid-Based Micelles as Ocular Platform to Modulate the Loading, Release, and Corneal Permeation of Corticosteroids.

The aim of this work is to prepare hyaluronic acid-based micelles as a platform to load corticosteroid drugs and to improve their corneal permeation after administration on the ocular surface. Three amphiphilic derivatives of hyaluronic acid (HA) are synthesized using different amounts of hexadecylamine (C16 -NH2 ). HAC16 a, HAC16 b, and HAC16 c derivatives are able to form micelles by the cosolvent evaporation method and to entrap corticosteroids (dexamethasone, triamcinolone, triamcinolone acetonide). HAC16 a and HAC16 b micelles show the best results in terms of drug loading and particle size. They are also able to improve drug release compared to free drug solution or suspension. In addition, HAC16 b micelles show an optimal mucoadhesion and compatibility with human corneal epithelial cells. In vitro and ex vivo permeation studies of drug-loaded HAC16 b micelles are performed to understand the ability of these micelles to act as penetration and/or permeation enhancers.

RP-HPLC method with fluorescence detection for determination of small quantities of triamcinolone in plasma in presence of endogenous steroids after derivatization with 9-anthroyl nitrile; pharmacokinetic studies.

A new indirect RP-HPLC method was developed for determination of small, ng/ml, concentrations of triamcinolone (TMC) in human plasma, in presence of endogenous corticosteroids: cortisol (hydrocortisone, F), cortisone (E) and their metabolites, after administration of TMC in a free alcohol form. After solid phase extraction (SPE) in cartridges with octadecyl phase, TMC and prednisolone (I.S.) were derivatized by treatment with 9-anthroyl nitrile (9-AN) in a basic mixture, consisting of triethanolamine and quinuclidine, to receive fluorescent esters at 21-hydroxyl group of the steroid chain. Optimal conditions were also established to purify fluorescent TMC and I.S. derivatives before injection into HPLC column. The fluorescent esters were determined using an isocratic RP-HPLC technique in a C18 column. The mobile phase consisted of acetonitrile and 0.3 mM ortho-phoshoric acid. The method was validated before using to pharmacokinetic studies. Calibration curve of TMC was linear in the range of 2.5-100.0 ng/ml. Intra- and inter-day measurement precision and accuracy were equal to or lower than 15%. Percent recovery, and limits of detection (LOD) and quantification (LOQ) of TMC were also determined. The method was applied for in vivo conditions after administration of tablets containing TMC to healthy volunteers. Moreover, the method provided potential to determine TMC and, simultaneously, other glucocorticoids: E, F and their metabolites in one analytical run. Column interactions were observed between endogenous metabolites of E. Usefulness of the elaborated method was confirmed in pharmacokinetic studies following administration of a small (4 mg) dose of TMC to human volunteers. The method can provide an alternative to HPLC coupled with RIA in determination of small quantities of TMC.

Hyaluronic acid based micelle for articular delivery of triamcinolone, preparation, in vitro and in vivo evaluation.

A novel triamcinolone loaded polymeric micelle was synthesized based on hyaluronic acid and phospholipid for articular delivery. The newly developed micelle was characterized for physicochemical properties including size, zeta potential, differential scanning calorimetry (DSC) analysis and also morphology by means of transmission electron microscopy. The biocompatibility of micelle was explored by histopathological experiment in rat model. Also biological fate of micelle was investigated in rat by means of real time in vivo imaging system. Triamcinolone loaded micelle was in the size range of 186 nm with negative zeta potential charge. Micelles were spherical in shape with core shell like structure. Triamcinolone was released from micelle during 76 h with almost low burst effect. DSC analysis showed the conversion of crystalline triamcinolone from its crystalline state. Histopathological analysis showed no evidence of tissue damage or phagocytic accumulation in knee joint of rat. The real time in vivo imaging analysis suggested at least three days retention time of micellar system in knee joint post injection.

Intra-articular corticosteroids. Guide to selection and indications for use.

Physicians have used intra- and periarticular corticosteroids for treating a variety of rheumatic diseases for nearly 50 years. Yet publications that have carefully examined the mechanisms of action, the pharmacokinetics and the comparative safety and efficacy of the available agents are sparse. This limits our ability to choose a drug scientifically. Similarly, we know little about the long term outcomes of joints infected with corticosteroids versus those not injected. Highly branched esters of methylprednisolone or triamcinolone are the preferred agents used by American rheumatologists. Pharmacokinetic studies reveal that triamcinolone hexacetonide, the least soluble of all the corticosteroid esters, is retained in the joint for 2 to 3 weeks. Intra-articular corticosteroids may implement their anti-inflammatory effect by down-regulating genetic expression of several pro-inflammatory proteins. A literature review suggests that judicious use of intra- and periarticular corticosteroids is very helpful in temporarily reducing pain and inflammation in musculoskeletal structures and may facilitate increased motion and function in selected cases. Their use in juvenile arthritis also appears to be safe and beneficial. Infection in or about the joint in the chief contraindication to use. Adverse effects are very few but the number of injections per joint should probably be limited to 4 or less per year.

An intravitreal sustained-release triamcinolone and 5-fluorouracil codrug in the treatment of experimental proliferative vitreoretinopathy.

OBJECTIVE: To determine the efficacy and pharmacokinetics of an intravitreal sustained-release triamcinolone acetonide and 5-fluorouracil (TA/5-FU) codrug in the treatment of experimental proliferative vitreoretinopathy (PVR). METHODS: The therapeutic efficacy of the TA/5-FU codrug was determined in a rabbit model that simulates human PVR. Intravitreal levels of triamcinolone and 5-fluorouracil were measured at different time points and drug release in vitro was tested. Toxic effects were evaluatedby electroretinograpy, clinical examination, and light microscopy. RESULTS: Both the severity of PVR grade and the percentage of eyes with moderate or worse tractional detachment were significantly less in eyes treated with the codrug. The therapeutic effect of the intravitreal codrug was paralleled by sustained intravitreal levels of triamcinolone and 5-fluorouracil. There were no drug-related toxic effects evident on clinical or histopathologic examination of eyes containing the TA/5-FU codrug. CONCLUSIONS: The intravitreal sustained-release TA/5-FU codrug effectively inhibits the progression of PVR in a rabbit model that closely resembles PVR in humans. The TA/5-FU codrug may simultaneously target different components of the wound-healing response.

Receptor-based pharmacokinetic-pharmacodynamic analysis of corticosteroids.

The pharmacodynamics of three corticosteroids were investigated after intravenous administration of the phosphate esters of methylprednisolone, dexamethasone, and triamcinolone acetonide to healthy subjects at 20, 50, and 80 mg as well as placebo. Twenty-two different pharmacodynamic parameters were followed as a function of time for 48 hours. Statistically significant effects of the glucocorticoids were an increase in blood glucose levels, a decrease in the number of lymphocytes, eosinophils, basophils, and monocytes, and an increase in the number of granulocytes and stab cells. For the most significant pharmacodynamic effects (lymphocytes, granulocytes, and glucose) a previously derived integrated pharmacokinetic/pharmacodynamic model using plasma concentrations, protein-binding data, and in vitro receptor-binding affinities was used to predict the pharmacodynamic effect-time profiles. Good agreement of predicted and measured effects was observed, confirming the validity of the model. The clinical significance of the model was demonstrated by comparison of model-predicted maintenance doses with empirically determined clinical equivalency doses.

Development of a multiple-drug delivery implant for intraocular management of proliferative vitreoretinopathy.

A prototype multiple-drug delivery implant has been developed for the intraocular management of proliferative vitreoretinopathy (PVR). Because of the recurrent nature of the disease, PVR causes blindness in approximately 7% of patients who have undergone retinal re-attachment surgery. The poly(dl-lactide-co-glycolide) 50/50 (PLGA) implant consists of three cylindrical segments, each of which contains one of the following drugs: 5-fluorouridine (5FUrd, an antimetabolite), triamcinolone (Triam, a corticosteroid), and human recombinant tissue plasminogen activator (t-PA, a thrombolytic agent). The device can be inserted through a 20-gauge syringe needle into the vitreous body of the eye. The implant also possesses a PLGA coating over the t-PA-containing terminal segment, which creates a lag-time to deliver t-PA when most needed and to decrease the risk of postoperative bleeding. Two methods of cylinder fabrication were investigated: heat and solvent extrusion. The release behavior of several drugs was examined as a function of the processing variables including: extrusion method, drug loading, polymer molecular weight, and drug particle size. The presence of either the organic solvent (acetone) during processing or a highly water-soluble drug (5FUrd) in the formulation increased the polymer porosity, which in turn, increased the drug release-rate. Drug loading effects were consistent with percolation concepts, and a low-molecular-weight PLGA (e.g., Mw=42000 for inherent viscosity=0.58 dl/g) was desirable to produce controlled release close to one month. Based on pharmacological and pharmacokinetic data of these compounds and our clinical experience with this disease, several design criteria for a combined implant were devised. Optimal cylindrical segments from the formulation studies were selected and combined in series to form a contiguous implant. After successful combination and coating procedures were developed, prototype implants were prepared. From the 3-drug prototype, 5FUrd and Triam were released approximately 1 microgram/day for over 4 weeks and 10-190 microgram/day over 2 weeks, respectively. The solvent-extrusion procedure did not significantly alter the stability of the encapsulated t-PA (>94+/-5% serine protease activity after preparation). After a lag-time of approximately 2 days, t-PA was released active at a rate of approximately 0.2-0.5 microgram/day in approximately 2 weeks. The release characteristics from the combined implant largely met our initial design criteria. Hence, controlled-release implants of this kind may have potential use for intraocular treatment of PVR.

[Thermographic study of the percutaneous absorption of corticosteroids]. / Studio termografico sull'assorbimento percutaneo dei corticosteroidi.

The results of a study on the percutaneous absorption of two corticosteroids, Halcinonide at 0.1% and Triamcinolone acetonide at 0.1%, employing an original thermographic method, are reported. In a first group of subjects treated with one application of the two corticosteroids a stronger activity of the Halcinonide was found than in a second group of subjects, after repeated applications, resulting progressively more evident and of longer duration in comparison with Triamcinolone.

Different intravitreal properties of three triamcinolone formulations and their possible impact on retina practice.

PURPOSE: We sought to better characterize the intravitreal profile of different triamcinolone formulations. METHODS: The study was performed in vitro and in vivo. Kenalog-40, Triesence, and Transton were characterized for ocular pharmacokinetics, particle size, crystallinity, and dissolving kinetics in vitreous following an intravitreal injection into 12 rabbit eyes. The relationship of free drug levels in the aqueous and vitreous was investigated through a dual-probe microdialysis and liquid chromatography tandem mass spectrometry. RESULTS: Triesence had the most uniform particle size distribution (mean 11.51 µm) and Kenalog-40 had the largest particle sizes (mean 18.86 µm). Triesence and Kenalog-40 had 100% crystallinity, while Transton had 89% crystallinity. Triesence had a slower dissolution in vitreous than that of Kenalog-40, and Transton had the fastest dissolution, though their solubility was very similar. Following a 1.2 mg intravitreal injection in the rabbit eye, Triesence had a significantly lower ocular free drug level than Kenolog-40 (P = 0.025) and Transton (P = 0.007). Quantitative dual-probe microdialysis revealed that the aqueous free triamcinolone (Kenolog-40) was less than 1% of the vitreous free triamcinolone during the first few hours, and this percentage increased to 26.8% at 2 weeks and was 11.7% at 3 weeks following an intravitreal injection. CONCLUSIONS: Triesence demonstrated a significantly slower dissolution profile and lower free drug level in the vitreous than the other preserved triamcinolone, which may translate into a longer therapeutic duration and lower rate of drug-associated complications.

Endoscopic neural blockade for rhinogenic headache and facial pain: 2011 update.

BACKGROUND: Over 45 million Americans suffer from recurrent headaches, and an estimated $11.9 million was spent on doctor's visits for rhinogenic pain last year. Sphenopalatine blocks have been described for various facial pain syndromes, but their use and the type of blockade agents remain controversial. The objective of this study was to demonstrate that endoscopic nerve blocks, using a mixture of bupivicaine and triamcinolone-40, injected into the anterior ethmoid or sphenopalatine regions, can be a relative safe and effective option for refractory pain. METHODS: The charts of all patients undergoing endoscopic neural blockade, in a private practice setting from 1998 to 2008 were retrospectively reviewed. A 1:1 mixture of 0.5% bupivicaine and triamcinolone acetonide injectable suspension was injected into the patients' anterior ethmoid or sphenopalatine neural distribution, or both, depending on the pain distribution. Charts were reviewed to assess outcomes and any adverse events from nerve blocks. RESULTS: A total of 882 nerve blocks were administered to 147 patients, over the course of 431 office visits. Four mild complications, 2 moderate complications, and no severe or permanent complications were noted. No permanent visual complications were observed. Of all the charts, 85% had documented effects of the nerve block at follow-up. Of those, 81.3% claimed improvement, 17.9% reported feeling the same, and 0.79% stated they had worse pain. CONCLUSION: Endoscopic neural blockade appears to be a relatively safe and viable option in the treatment of refractory headache and facial pain with a rhinogenic component.

Determination of triamcinolone in human plasma by a sensitive HPLC-ESI-MS/MS method: application for a pharmacokinetic study using nasal spray formulation.

A liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) method for the quantitation of triamcinolone in human plasma after nasal spray application was developed and validated. Betamethasone was used as internal standard (IS). The analytes were extracted by a liquid-liquid procedure and separated on a Zorbax Eclipse XDB C(18) column with a mobile phase composed of 2 mM aqueous ammonium acetate pH 3.2 and acetonitrile (55:45). Selected reaction monitoring was performed using the transitions m/z 435 → 415 and m/z 393 → 373 to quantify triamcinolone acetonide and betamethasone, respectively. Calibration curve was constructed over the range of 20-2000 pg/ml for triamcinolone acetonide. The lower limit of quantitation was 20 pg/ml. The mean RSD values were 4.6% and 5.7% for the intra-run and inter-run precision, respectively. The mean accuracy value was 98.5% and a recovery rate corresponding to 97.5% was achieved. No matrix effect was detected in the samples. The validated method was successfully applied to determine the plasma concentrations of triamcinolone acetonide in healthy volunteers, in a pharmacokinetic study with nasal spray formulation.