Ahmed S. Saad

A smart simple spectrophotometric method for simultaneous determination of binary mixtures

A new simple spectrophotometric method was developed for the simultaneous determination of drugs with interfering spectra in binary mixtures without previous separation. The new method is based on a simple modification for the ratio subtraction method. This modification enabled wider range of application. The proposed ratio difference method was applied for the determination of brimonidine and timolol in laboratory prepared mixtures with mean percentage recoveries 100.40±2.29 and 101.23±1.30 respectively, and in their pharmaceutical formulation with mean percentage recoveries 101.08±0.44 and 100.66±0.52 respectively. The suggested ratio difference method was validated according to USP guidelines and can be applied for routine quality control testing.

Enthesitis and Related Changes in the Knees in Seronegative Spondyloarthropathies and Skin Psoriasis: Magnetic Resonance Imaging Case-Control Study

Objective. To describe enhanced magnetic resonance imaging (MRI) features and characteristic entheseal changes in the knees in patients with seronegative spondyloarthropathy (SpA). Methods. The 56 patients included 30 with psoriatic arthritis, 5 with ankylosing spondylitis, 5 with reactive arthritis, 5 with ulcerative colitis (UC), 5 with Crohn’s disease, and another 6 with skin psoriasis. Controls were 20 healthy subjects without knee complaints. MRI was performed in all participants, emphasizing entheseal sites. Results. Both knees were studied in 45 (80.3%) patients and one knee in 11 (19.6%). MRI showed evidence of bone marrow edema in 13 (23.2%) patients, cartilaginous erosions in 18 (32.1%), and bone erosions in 9 (16.1%). Enthesitis was found in medial collateral ligaments in 18 (32.1%), lateral collateral ligaments in 8 (14.3%), posterior cruciate ligaments in 3 (5.35%), patellar tendon in 18 (32.1%), biceps femoris insertion in 3 (5.35%), medial patellofemoral ligaments (MPFL) in 5 (8.9%), and lateral patellofemoral ligament in 1 patient (1.8%). In the UC and Crohn’s patients (n = 10), 2 had bone erosions and 5 had enthesitis. In the skin psoriasis group (n = 6), one had bone marrow edema; enthesitis was detected in 5 at the patellar tendon insertion and in one in the MPFL. Entheseal-related changes were absent in the controls. Conclusion. This is the first study showing entheseal-related changes in the knees in patients with inflammatory bowel disease or skin psoriasis without clinical arthritis. Enthesitis of the knee on MRI may be an early finding in SpA.

Knee Enthesitis and Synovitis on Magnetic Resonance Imaging in Patients with Psoriasis without Arthritic Symptoms

Objective. This case-control study was designed to evaluate magnetic resonance imaging (MRI) findings of knee joints in patients with psoriasis without clinical peripheral or axial joint involvement, and to correlate MRI findings with disease and demographic variables. Methods. In total 48 patients with psoriasis and no clinical evidence of synovitis or enthesitis in any peripheral or axial joints were enrolled. A random sample of 20 healthy subjects without knee or other joint complaints and matched for age and sex served as controls. All patients and controls underwent enhanced MRI studies of both knee joints, and MRI findings were compared. Results. Among 48 patients (96 knees), a total of 90 entheseal lesions were detected, with no enthesitis in 2 cases (6.3%). Signs of continuing inflammation bilaterally were frequently found: soft tissue edema (STE; n = 52), bone marrow edema (BME; n = 20), perientheseal BME (n = 3), cartilaginous erosions (n = 42), and bone erosions (n = 27). In controls, 2 (10%) subjects had BME and another 5 (25%) showed cartilaginous erosions. None showed evidence of enthesitis. Significant correlations were observed between the number of entheseal lesions of both knees vs STE (present vs absent; r = 0.314, p = 0.030) and STE (number of lesions; r = 0.351, p = 0.014). Enthesitis (unilateral vs bilateral) was significantly and positively correlated with STE (r = 0.304, p = 0.036), cartilaginous erosions (r = 0.304, p = 0.036), and villous projections (r = 0.347, p = 0.016). Conclusion. Subclinical synovitis and enthesitis are frequently found in the knee joint of patients with psoriasis. These may be an early sign of psoriatic arthritis.

Combining the isoabsorptive point in the ratio spectrum and the smart ratio difference methods for a single step determination of compounds with overlapped spectra

A new method significantly advantageous over the conventional spectrophotometric methods regarding simplicity, minimal data processing and applicability was developed. The new method is based on the fact that isoabsorptive points whenever present in an absorption spectrum will be retained even after division by a one component as a divisor in the ratio spectrum, in addition to a smart modification of the conventional ratio derivative and ratio subtraction methods. This modified method though simpler, enabled wider range of applications. The proposed method was applied for the analysis of brimonidine and timolol in laboratory prepared mixtures with mean percentage recoveries 100.64 ± 1.10 and 100.96 ± 1.16, respectively, and in their pharmaceutical formulation with mean percentage recoveries 100.88 ± 0.34 and 100.84 ± 0.72, respectively. The suggested method was validated according to USP guidelines and can be applied for routine analysis in quality control laboratories.

Can Magnetic Resonance Imaging Differentiate Undifferentiated Arthritis Based on Knee Imaging

Objective. To compare findings as observed on enhanced magnetic resonance imaging (MRI) of the knee joints, in oligoarticular-undifferentiated arthritis (UA) in those with established rheumatoid arthritis (RA) and spondyloarthropathy (SpA). Methods. A total of 55 patients with knee arthritis were consecutively recruited for the study, including 25 with undifferentiated oligoarthritis of the knee joint(s), 15 fulfilling the American College of Rheumatology criteria for RA and 15 with SpA. Laboratory investigations included erythrocyte sedimentation rate, C-reactive protein, complete blood count, aspartate aminotransferase, alanine aminotransferase, serum creatinine, and urine analysis. In all patients in the UA and in the RA group, rheumatoid factor and anti-CCP2 antibody (ELISA) were tested. All patients underwent enhanced MRI of the more symptomatic knee. All groups were compared in terms of demographics, laboratory investigations, and MRI findings. Results. Synovial thickness differed significantly in the RA group compared to UA and SpA groups (p < 0.001). The RA group showed a higher rate of bony and cartilaginous erosions and bone marrow edema compared to UA and SpA groups (p < 0.001). Enthesitis was found in all patients in the SpA group (100%) and differed from RA and UA groups (p < 0.001). Conclusion. Patients with RA showed more destructive changes in terms of synovial thickening, bone marrow edema, cartilaginous and bone erosions compared to UA and SpA groups. Enthesitis is a common feature on MRI in SpA, while absent in the RA and UA groups. This latter finding may have important clinical implications for classification purposes, and can help to determine the evolving pattern of patients with UA of the knee joint.

A Novel Simple Method for Resolving Overlapped Spectral Data with A Wide Range of Applicability, and Its Application as a Stability Indicating Method for Determination of Tazarotene

Smart simple spectrophotometric method was developed for simultaneous determination of compounds with interfering spectra in binary mixtures without previous separation. The proposed method showed significant advantages over the conventional methods regarding minimal data manipulation and applicability. The new method is based on a modification for the ratio subtraction and derivative ratio methods. This modification enabled wider range of application. The proposed method was applied for the determination of tazarotene and its alkaline degradation product in laboratory prepared mixtures with mean percentage recoveries 99.68 ± 1.36 and 100.86 ± 1.09 respectively. The suggested method was validated according to USP guidelines and can be applied for routine quality control testing.

Novel spectrophotometric method for selective determination of compounds in ternary mixtures (dual wavelength in ratio spectra).

A simple selective spectrophotometric method for determination of compounds in ternary mixture was developed by combining the resolution power of two well-known methods that are commonly used for binary mixtures; namely ratio difference method and dual wavelength. The new method (dual wavelength in ratio spectra) was successfully applied for the determination of a ternary mixture of betamethasone dipropionate (BM), clotrimazole (CT) and benzyl alcohol (BA) in pure powder form and in their pharmaceutical preparation. The difference in amplitudes (ΔP) in the ratio spectra at 252.0 and 258.0 nm (ΔP(252.0-258.0 nm)) corresponds to BM, while ΔP(266.8-255.4 nm) and ΔP(254.2-243.5 nm) corresponds to CT and BA, respectively. The method was validated as per the USP 2005 guidelines. The developed method can be used in quality control laboratories for routine analysis of compounds in ternary mixtures.

Novel ratio difference at coabsorptive point spectrophotometric method for determination of components with wide variation in their absorptivities.

Different methods have been introduced to enhance selectivity of UV-spectrophotometry thus enabling accurate determination of co-formulated components, however mixtures whose components exhibit wide variation in absorptivities has been an obstacle against application of UV-spectrophotometry. The developed ratio difference at coabsorptive point method (RDC) represents a simple effective solution for the mentioned problem, where the additive property of light absorbance enabled the consideration of the two components as multiples of the lower absorptivity component at certain wavelength (coabsorptive point), at which their total concentration multiples could be determined, whereas the other component was selectively determined by applying the ratio difference method in a single step. Mixture of perindopril arginine (PA) and amlodipine besylate (AM) figures that problem, where the low absorptivity of PA relative to AM hinders selective spectrophotometric determination of PA. The developed method successfully determined both components in the overlapped region of their spectra with accuracy 99.39±1.60 and 100.51±1.21, for PA and AM, respectively. The method was validated as per the USP guidelines and showed no significant difference upon statistical comparison with reported chromatographic method.

Comparative study on the selectivity of various spectrophotometric techniques for the determination of binary mixture of fenbendazole and rafoxanide

Five different spectrophotometric methods were applied for simultaneous determination of fenbendazole and rafoxanide in their binary mixture; namely first derivative, derivative ratio, ratio difference, dual wavelength and H-point standard addition spectrophotometric methods. Different factors affecting each of the applied spectrophotometric methods were studied and the selectivity of the applied methods was compared. The applied methods were validated as per the ICH guidelines and good accuracy; specificity and precision were proven within the concentration range of 5-50 μg/mL for both drugs. Statistical analysis using one-way ANOVA proved no significant differences among the proposed methods for the determination of the two drugs. The proposed methods successfully determined both drugs in laboratory prepared and commercially available binary mixtures, and were found applicable for the routine analysis in quality control laboratories.

Stability-indicating chemometric methods for the determination of tazarotene

Two multivariate calibration methods-principal component regression (PCR) and partial least square (PLS)-have been used to determine tazarotene in the presence of its degradation products. Both methods are useful in spectral analysis because of the simultaneous inclusion of many spectral wavelengths instead of the single wavelength used in derivative spectrophotometry. A great improvement in the precision and predictive abilities of these multivariate calibrations was observed. A calibration set was constructed for the mixture and the best model was used to predict the concentration of the selected drug. The proposed methods were applied successfully in the determination of tazarotene in laboratory-prepared mixtures and in commercial preparations. Tazarotene was analyzed with mean accuracies of 100.006 ± 0.695 and 100.007 ± 0.690 using the PCR and PLS methods, respectively. The validity of the proposed methods was assessed using the standard addition technique. The proposed methods were found to be rapid, simple and required no preliminary separation. They can therefore be used for the routine analysis of tazarotene in quality-control laboratories.