Quality Evaluation of Gentamicin Sulfate Reference Standards in Japanese Pharmacopoeia Using Hydrophilic Interaction Chromatography Combined With Tandem Mass Spectrometry.

BACKGROUND: Through the recent development of analytical technology, antibiotics quantification in the Japanese Pharmacopoeia (JP) has changed from traditional microbiological assays to physicochemical methods with high specificity and precision. However, for several multicomponent antibiotics without typical UV absorption, potency cannot be directly determined using instrumental methods such as high-performance liquid chromatography; therefore, traditional microbiological assays are still used. Gentamicin sulfate (GmS), which consists of three major components, C1, C1a, and C2, is such a typical antibiotic, and its antimicrobial potency continues to be assayed using microbiological methods in JP monographs. Introduction of a physicochemical assay for GmS is needed to help ensure its quality and quantity. OBJECTIVE: This study aimed to develop quality control measures for GmS that could be complementary to quantitative assays and purity tests specified in the JP. METHODS: For each gentamicin C component (C1, C2, and C1a), theoretical potencies were determined based on the quantitative relationship between purity and potency, as measured by quantitative 1H NMR and microbiological assays, respectively. Two lots of the JP reference standard (RS) were used as test samples, with the contents of each component and impurity (sisomicin and garamine) being determined using hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS). RESULTS: The ratios of theoretical potency for C1, C2, and C1a were 1.00, 1.21, and 1.80, respectively. The potencies of the GmS JP RSs, which were estimated based on the contents and theoretical potency of each C component, corresponded well with those determined through microbiological assays. Marked differences in impurities (%) between the two RS lots were highlighted by quantifying sisomicin and garamine. CONCLUSIONS: The developed analytical procedure enabled the characterization of two different JP RSs in terms of content ratio, potencies, and impurities. HIGHLIGHTS: Novel analytical procedures useful for routine quality control of GmS were developed using HILIC-MS/MS.

[TRANSVERSE TESTICULAR ECTOPIA WITH INCIDENTAL TESTICULAR TUMOR, DISCOVERED UPON SYMPTOMATIC TESTICULAR TORSION].

Transverse testicular ectopia is a condition in which a testicle crosses the midline and descends through the contralateral inguinal canal, with both testes in the same scrotal compartment. It is reported to be present in about 2% of persons who present with non-palpable testicles. Most transverse testicular ectopia patients undergo orchiopexy in early childhood; however, in rare cases, they are diagnosed in adulthood upon detection of testicular tumors.A 40-year-old man visited our hospital complaining of right abdominal pain. His right testis was palpable in the right scrotum; however, the left scrotal compartment seemed empty and there was a painful mass on the upper part of the right scrotal compartment. Computed tomography showed that both spermatic cords traversed through the right inguinal canal, and transverse testicular ectopia was diagnosed. Ultrasonography showed absent left testicular circulation on the upper part of the right scrotum. Upon diagnosis of left testicular torsion, emergency surgery was conducted. In the right scrotum, there was a normal right testicle, and a necrotic left testicle which was twisted 180 degrees on its axis, towards the cranial side. Histopathology of the excised left testicle revealed an incidental seminoma, pT1. Tumor markers following surgery were negative, and there was no evidence of recurrence observed with two years and five months of follow-up.Non-palpable testicular torsion may also be a transverse testicular ectopia. Therefore, it is necessary to consider malignant tumors based on the patient's age.

[SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE SECRETION AS A SIDE EFFECT OF CHEMOTHERAPY FOR URACHAL CARCINOMA: A CASE REPORT].

A 54-year-old woman was admitted to our hospital complaining of gross hematuria and difficulty urinating. Cystoscopy revealed a tumor 4 cm in size with calcification on top of the bladder. After diagnosis of urachal carcinoma by transurethral resection of the bladder, partial cystectomy with en bloc resection of the median umbilical ligament and pelvic lymphadenectomy was performed. Pathological diagnosis confirmed urachal carcinoma, pT3b, ly1, v0, pN1, RM0. TS-1 and cisplatin chemotherapy (TS-1 at 100 mg/day on days 1-21, CDDP at 60 mg/m2 on day 8) was administered. On day 13, the patient was admitted because of consciousness disorder (Glasgow Coma Scale E2V1M4). Hyponatremia (Na 109 mEq/l) and renal excretion of sodium were present and the patient was diagnosed with the syndrome of inappropriate antidiuretic hormone secretion (SIADH) induced by chemotherapy. Serum sodium level and her consciousness level gradually improved after administration of 3% saline. SIADH caused by chemotherapy containing cisplatin is a relatively rare, but potentially serious adverse effect that requires close attention.