An Observational Study of Cutaneous Manifestations in Patients on Chemo and Radiation Therapy for Internal Malignancies at Tertiary Care Center.

Context: Chemotherapy and radiation therapy given to treat internal malignancies may cause cutaneous, hair, nail, and oral mucosal changes. The present study is an effort to know the pattern of cutaneous drug reactions with chemo and radiotherapy. Materials and Methods: Patients of internal malignancies with skin lesions attending the dermatology and oncology OPD/ward were recruited after taking their written consent in vernacular language. A detailed history of skin lesions, malignancies, and treatment was taken. Clinical examination was carried out. Relevant investigations and biopsy were carried out as and when required. Being a descriptive study, age group and gender-wise frequency and percentage were calculated for the treatment of malignancies and dermatosis. Results: The study included 150 patients with 28 different types of internal malignancies, of which 127 (84.66%) patients were treated, 45 (35.43%) treated exclusively with chemotherapy, 16 (12.59%) with exclusive radiation therapy, and 66 (51.96%) with combined chemo and radiation therapy. Total 111 (87.41%) patients received chemotherapy and 82 (64.56%) patients received radiation therapy. Most common internal malignancy was breast carcinoma in 43 (28.67%) cases. Most common chemotherapeutic agent given was paclitaxel to 33 (29.73%) patients. Most common dermatosis associated with exclusive chemotherapy was hand-foot syndrome in 7 (15.55%) cases and with exclusive radiation therapy was radiation dermatitis in 8 (50%) cases. Conclusions: The study was useful in understanding various chemo and radiation therapy-associated dermatosis so that early interventions can be done to prevent further treatment-related adverse effects. Limitation: Small sample size and inability of pinpointing a single drug as the side effect.

An Observational Study of Cutaneous Manifestations in Internal Malignancy at Tertiary Care Centre.

Introduction: Skin is the largest organ in the human body and mirrors the changes in the organism it envelops. Internal malignancies can cause various specific and non-specific cutaneous manifestations along with hair, nail and oral mucosal changes. Some of the changes are detected early indicating a strong association with cancer, while some occur in later stage indicating dissemination or immunosuppression. The present study is an effort to know pattern of dermatosis associated with internal malignancies so that early diagnosis and interventions can be done. Aim: To determine the pattern of specific and non-specific dermatosis associated with internal malignancy. Methods and Material: Patients of internal malignancies with skin lesions attending dermatology and oncology department during July 2020 to June 2021 were recruited in the study after taking written informed consent. A detailed history of skin lesions and malignancies were taken. Clinical examination (skin/hair/nail) was carried out and photographs were taken. Relevant investigations were carried out. Frequency and percentage of dermographic data and dermatosis associated with internal malignancies were calculated. Results: The study included 150 patients with maximum number of patients 78 (52%) in 41-60 years of age group with female: male ratio of 1.2:1. Most common internal malignancy was breast carcinoma in 43 (28.67%) cases. Specific dermatosis were seen in 5 (3.33%) cases and non-specific dermatosis in 121 (80.66%) cases. Specific dermatosis were vasculitis, necrolytic migratory erythema, lymphocytoma cutis, growth and cutaneous metastasis with 1 (0.67%) patient each. Most common non-specific dermatosis was herpes zoster in 17 (11.33%) cases. Conclusion: The study was useful in understanding the various specific and non specific dermatosis associated with internal malignancies and thereby helping the physician to manage the conditions.

Quantitation of tadalafil in human plasma using a sensitive and rapid LC-MS/MS method for a bioequivalence study.

A highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of tadalafil (TAD) in human plasma. TAD and its deuterated internal standard (IS), tadalafil-d3, were extracted from 200 µL plasma using Phenomenex Strata-X-C 33 µ extraction cartridges. Chromatographic analysis was carried out on Synergi™ Hydro-RP C18 (100 mm × 4.6 mm, 4 µm) column with a mobile phase consisting of methanol and 10 mM ammonium formate, pH 4.0 (90:10, v/v), delivered at a flow rate of 0.9 mL/min. Quantitation of the protonated analyte was done on a triple quadrupole mass spectrometer using multiple reaction monitoring via electrospray ionization. The precursor to product ions transitions monitored for TAD and TAD-d3 were m/z 390.3 → 268.2 and m/z 393.1 → 271.2, respectively. The calibration curve was linear over the concentration range of 0.50-500 ng/mL with correlation coefficient, r2 ≥ 0.9994. Acceptable intra-batch and inter-batch precision (≤ 3.7%) and accuracy (97.8% to 104.1%) were obtained at five concentration levels. The recovery of TAD from spiked plasma was highly precise and quantitative (98.95% to 100.61%). Further, the effect of endogenous matrix components was minimal. TAD was found to be stable under different storage conditions in human plasma and also in whole blood samples. The validated method was successfully used to determine TAD plasma concentration in a bioequivalence study with 20 mg TAD tablets in 24 healthy volunteers. Method performance was evaluated by reanalyzing 115 study samples.

Sensitive and rapid determination of amantadine without derivatization in human plasma by LC-MS/MS for a bioequivalence study.

A highly sensitive, rapid and rugged liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for reliable estimation of amantadine (AMD), an antiviral drug in human plasma. The analyte and internal standard (IS), amantadine-d6 (AMD-d6), were extracted from 200 µL plasma by solid phase extraction on Phenomenex Strata-X-C 33 µ cartridges. Chromatography was performed on Synergi™ Hydro-RP C18 (150 mm × 4.6 mm, 4 µm) analytical column using a mixture of acetonitrile and 10 mM ammonium formate, pH 3.0 (80:20, v/v) as the mobile phase. Detection and quantitation was done by multiple reaction monitoring in the positive ionization mode for AMD (m/z 152.1 → 135.1) and IS (m/z 158.0 → 141.1) on a triple quadrupole mass spectrometer. The assay was linear in the concentration range of 0.50-500 ng/mL with correlation coefficient (r2) ≥ 0.9969. The limit of detection of the method was 0.18 ng/mL. The intra-batch and inter-batch precisions were ≤ 5.42% and the accuracy varied from 98.47% to 105.72%. The extraction recovery of amantadine was precise and quantitative in the range of 97.89%-100.28%. IS-normalized matrix factors for amantadine varied from 0.981 to 1.012. The stability of AMD in whole blood and plasma was evaluated under different conditions. The developed method was successfully applied for a bioequivalence study with 100 mg of AMD in 32 healthy volunteers. The reproducibility of the assay was determined by reanalysis of 134 subject samples.

Quantitation of tadalafil in human plasma using a sensitive and rapid LC-MS/MS method for a bioequivalence study / 药物分析学报

A highly sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of tadalafil (TAD) in human plasma. TAD and its deuterated internal standard (IS), tadalafil-d3, were extracted from 200 μL plasma using Phenomenex Strata-X-C 33 μ extraction cartridges.Chromatographic analysis was carried out on Synergi? Hydro-RP C18 (100mm × 4.6 mm, 4 μm) column with a mobile phase consisting of methanol and 10mM ammonium formate, pH 4.0 (90:10, v/v),delivered at a flow rate of 0.9 mL/min. Quantitation of the protonated analyte was done on a triple quadrupole mass spectrometer using multiple reaction monitoring via electrospray ionization. The precursor to product ions transitions monitored for TAD and TAD-d3 were m/z 390.3 → 268.2 and m/z 393.1 → 271.2, respectively. The calibration curve was linear over the concentration range of 0.50-500 ng/mL with correlation coefficient, r2 ≥ 0.9994. Acceptable intra-batch and inter-batch precision (≤3.7％) and accuracy (97.8％ to 104.1％) were obtained at five concentration levels. The recovery of TAD from spiked plasma was highly precise and quantitative (98.95％ to 100.61％). Further, the effect of endogenous matrix components was minimal. TAD was found to be stable under different storage conditions in human plasma and also in whole blood samples. The validated method was successfully used to determine TAD plasma concentration in a bioequivalence study with 20 mg TAD tablets in 24 healthy volunteers. Method performance was evaluated by reanalyzing 115 study samples.

Sensitive and rapid determination of amantadine without derivatization in human plasma by LC–MS/MS for a bioequivalence study / 药物分析学报

A highly sensitive, rapid and rugged liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for reliable estimation of amantadine (AMD), an antiviral drug in human plasma. The analyte and internal standard (IS), amantadine-d6 (AMD-d6), were extracted from 200 μL plasma by solid phase extraction on Phenomenex Strata-X-C 33 μ cartridges. Chromatography was performed on Synergi? Hydro-RP C18 (150 mm × 4.6 mm, 4 μm) analytical column using a mixture of acetonitrile and 10 mM ammonium formate, pH 3.0 (80:20, v/v) as the mobile phase. Detection and quantitation was done by multiple reaction monitoring in the positive ionization mode for AMD (m/z 152.1 → 135.1) and IS (m/z 158.0 → 141.1) on a triple quadrupole mass spectrometer. The assay was linear in the concentration range of 0.50–500 ng/mL with correlation coefficient (r2) ≥ 0.9969. The limit of detection of the method was 0.18 ng/mL. The intra-batch and inter-batch precisions were ≤ 5.42% and the accuracy varied from 98.47% to 105.72%. The extraction recovery of amantadine was precise and quantitative in the range of 97.89%–100.28%. IS-normalized matrix factors for amantadine varied from 0.981 to 1.012. The stability of AMD in whole blood and plasma was evaluated under different conditions. The developed method was successfully applied for a bioequivalence study with 100 mg of AMD in 32 healthy volunteers. The re-producibility of the assay was determined by reanalysis of 134 subject samples.

Sensitive and rapid high-performance liquid chromatography tandem mass spectrometry method for estimation of fulvestrant in rabbit plasma.

A rapid and sensitive high-performance liquid chromatography and electrospray tandem mass spectrometry method was developed and validated for estimation of fulvestrant in rabbit plasma using liquid-liquid extraction. The separation and quantification of fulvestrant were achieved by reverse-phase chromatography on a Sunfire C18 column (50 x 2.1. i.d., 3.5 microm) with isocratic elution at a flow rate of 300 microL/min using norethistrone as an internal standard from 500 microL plasma sample. The method was validated over the concentration range from 0.092 to 16.937 ng/mL with a lower limit of detection of 0.023 ng/mL. The intra-day and inter-day accuracy and precision were within 10%. The recovery was 85 and 90% for fulvestrant and norethistrone respectively. The chromatographic run time was only 2.5 min.