Contact in context最新文献

Ceftriaxone for injection, USP is a sterile, semisynthetic, broad-spectrum cephalosporin antibiotic for intravenous or intramuscular administration. Ceftriaxone sodium is a white to yellowish crystalline powder which is readily soluble in water, sparingly soluble in methanol and very slightly soluble in ethanol. The color of ceftriaxone sodium solutions ranges from light yellow to amber, depending on the length of storage, concentration and diluent used. Each vial contains ceftriaxone sodium equivalent to 250 mg, 500 mg, 1 gram or 2 grams of ceftriaxone activity. Ceftriaxone sodium contains approximately 83 mg (3.6 mEq) of sodium per gram of ceftriaxone activity. Intra-lot variability was detected in the spectra of 6 vials of ceftriaxone sampled from one lot. One of the vials was more than 8.3 multidimensional SDs away from the center of the cluster of the other 5 vials from the same lot, suggesting that the manufacturing process may not be in a state of control. Interlot variability was detected between two lots of the drug using a subcluster detection test (r_tn=0.9629, r_ts=0.9148, p=0.02).

Meropenem for Injection, USP is a sterile, pyrogen-free, white to pale yellow crystalline powder and is supplied in vials containing sufficient meropenem to deliver 1 g for intravenous administration. The Drug Quality Task Force at the University of Kentucky has found variability in the near-infrared spectra of meropenem samples. The variability was found both within a lot (where one vial from six was 12.0 SDs from the other 5 vials) and between lots of the drug (where 8 vials were >3 SDs from the center of the library, and one of those was 6.1 SDs away from the center of the library). This variability was detected using a statistical analysis of the spectra that included principal component analysis (PCA) and the BEST metric. Inter-lot variability was assessed using a spectral library of 90 meropenem vials obtained from 15 lots of drug from the same manufacturer. The results suggest that the drug may have been manufactured while the manufacturing process was operating outside of a state of process control.

Methylprednisolone sodium succinate for injection, USP is an anti-inflammatory glucocorticoid. The active ingredient is methylprednisolone sodium succinate, which is the sodium succinate ester of methylprednisolone. The substance is a white or nearly white, odorless, hygroscopic, amorphous solid. It is highly soluble in water and alcohol, insoluble in chloroform, and only slightly soluble in acetone. This injectable form of the drug is indicated for the treatment of various conditions, including some allergic states, dermatologic, endocrine, gastrointestinal, hematologic, neoplastic, nervous system, ophthalmic, renal, respiratory, and rheumatic disorders. The analysis of a single lot of methylprednisolone sodium succinate revealed significant intra-lot variability in the near-infrared spectra. Differences were visually apparent in the absorbance peaks, particularly in the ranges of 4500 to 5000 cm^-1 and 6000 to 6500 cm^-1. Further examination of a zoomed-in region (7000 to 8500 cm^-1) showed two spectra that were statistically significant outliers, positioned at 4.4 and 5.9 standard deviations (SDs) from the center of the sample cluster. An analysis of a spectral library containing 242 vials of methylprednisolone sodium succinate from 26 different lots found significant interlot variability and statistically confirmed the presence of distinct subclusters. To statistically validate the visual findings, a subcluster detection algorithm was applied to the spectral data. The algorithm confirmed that two distinct groups exist within the spectral data. The measured correlation value (r_ts =0.8704) was below the 98% confidence level threshold (r_tn =0.9916), leading to the acceptance of the alternative hypothesis that more than one group is present.

Thyrotropin alfa is a recombinant heterodimeric glycoprotein that serves as a highly purified form of human thyroid stimulating hormone (TSH). It is produced through recombinant DNA technology within a genetically modified Chinese hamster ovary (CHO) cell line. The molecule is structurally complex, consisting of two non-covalently linked subunits: an alpha subunit (92 amino acid residues) with two N-linked glycosylation sites, and a beta subunit (118 residues) containing one N-linked glycosylation site. The resulting amino acid sequence is identical to that of human pituitary TSH. Thyrotropin alfa is supplied as a sterile, non-pyrogenic, white to off-white lyophilized product, intended for intramuscular (IM) administration after reconstitution with Sterile Water for Injection, USP. Each vial of Thyrogen contains 1.1 mg thyrotropin alfa, 36 mg mannitol, 5.1 mg sodium phosphate, and 2.4 mg sodium chloride. The intralot analysis of the 12 vials sampled from lot EY0155 revealed significant differences in the drug product within the same manufacturing lot, as evidenced by both spectral plots and multivariate analysis. The visual differences were observed in the following wavenumber regions: 4000 to 5000 cm^-1, 5150 cm^-1, and the 6700 cm^-1 regions. The differences seen at 5150 cm^-1 are very likely a difference in moisture content. 25% of the vials were flagged as outliers, with vials appearing 3.3, 3.8, and 5.3 SDs from the center of the cluster of 12 vials. The interlot analysis of a spectral library containing 171 vials from 18 different lots of thyrotropin alfa demonstrated tremendous variability in the near-infrared absorption profiles across the samples. Obvious differences were observed in the spectra of the library at several wavenumber regions, including around 5900 and 6650 cm^-1. The ratio between two peak sizes between 5900 and 5950 cm^-1 was dramatically variable. Differences were also noted around 4250, 4400, and 4540 cm^-1, and from 4700 to 4800 cm^-1. Only one vial was an outlier, appearing 7.8 SDs away from the center of the library spectral cluster. Some literature suggests differences in the spectra of vials may reflect differences in the stability and efficacy of the drug.

Abatacept is a medication administered through intravenous infusion. It is supplied as a sterile, white, preservative-free, freeze-dried powder. Each vial of drug contains 250 mg abatacept, maltose, monobasic sodium phosphate, and sodium chloride for administration. Abatacept is a fusion protein consisting of the extracellular domain of CTLA-4 linked to the modified Fc portion of human immunoglobulin G1. It is produced using recombinant DNA technology. Abatacept is indicated for moderately to severely active rheumatoid arthritis in adults and polyarticular juvenile idiopathic arthritis in pediatric patients 6 years of age and older. It can be used as monotherapy or in combination with other disease-modifying antirheumatic drugs or methotrexate. Inter-lot variability was detected in a library of 132 vials spread across 34 lots of abatacept-maltose for injection by the University of Kentucky Drug Quality Task Force. A subcluster detection test was run on 13 vials that were shown to be an outlier group (r_tn=0.9940, r_test=0.9551, r_lim=0.9865, p=0.02). Five of these vials individually appeared 4 or more standard deviations from the library cluster.

Chlorothiazide sodium for injection, USP, is a diuretic and antihypertensive medication in the form of a white or practically white, sterile, lyophilized powder. Each vial contains 500 mg of chlorothiazide sodium, equivalent to 500 mg of chlorothiazide, and 250 mg of mannitol as an inactive ingredient. The pH is adjusted with sodium hydroxide. Chlorothiazide sodium has a molecular weight of 317.71 amu. Since 2020 there have been multiple national shortages of chlorothiazide. Recent studies target chlorothiazide's low bioavailability, aiming to enhance it through nanoparticle production via a supercritical method. The drug's solubility in supercritical carbon dioxide (scCO₂) is vital, with measurements ranging from 0.417×10^-5 to 1.012×10^-5 mole fraction under specific conditions. Adding co-solvents, like ethanol, DMSO, and acetone, to scCO₂ boosts solubility, with ethanol proving most effective, enhancing solubility by 2.02-11.75 times. Intra-lot variability was discovered in a sample of a lot of chlorothiazide sodium by the University of Kentucky Drug Quality Task Force. Two vials of six screened in one lot were displaced from the center of the lot by 4.0 and 4.2 SDs, respectively. Inter-lot variability was confirmed in the near-IR spectra of 204 vials obtained from 28 different lots of chlorothiazide sodium. Using full spectrum BEST analysis 13 vials (6.4%) were outliers.

Azacitidine injections are used to treat specific types of blood cancers. They work by interfering with the growth of cancer cells. Azacitidine for injection is a nucleoside metabolic inhibitor indicated for the treatment of (a) Adult patients with the following FAB myelodysplastic syndrome (MDS) subtypes: Refractory anemia (RA) or refractory anemia with ringed sideroblasts (RARS) (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), and chronic myelomonocytic leukemia (CMMoL), and (b) Pediatric patients aged 1 month and older with newly diagnosed Juvenile Myelomonocytic Leukemia (JMML). Intra-lot variability was initially detected in one lot of azacitidine for injection in which 17% of the samples scanned in the lot were more than 5 multidimensional SDs from the center of the lot cluster. After the intra-lot variability was detected, inter-lot variability was measured in a spectral library comprising 8 lots of azacitidine for injection.

The University of Kentucky's Drug Quality Task Force (DQTF) conducted a study to perform consumer-level quality assurance screening of vasopressin injections used in their healthcare pharmacies. The primary objective was to identify potential quality defects by examining intralot and interlot variability using Raman spectrometry and statistical analyses. Raman spectra were collected noninvasively and nondestructively from vasopressin vials (n=51) using a Thermo Scientific Smartraman DXR3 Analyzer. Data processing techniques, including smoothing with cubic splines and Multiplicative Scatter Correction (MSC), were applied to prepare the spectra for analysis. Statistical analyses employed included the Bootstrap Error-Adjusted Single-sample Technique (BEST), Principal Component Analysis (PCA), and subcluster detection to assess variability and detect unusual samples. The study revealed significant intralot and interlot variability in the vasopressin samples. Analysis of Raman spectral graphs from vials in lot 22040L1C0 showed multiple subgroups within a single lot, indicating variability in chemical composition. Examination of the entire spectral library, which included vials from two different lot numbers, revealed four distinct groups that did not correspond to lot numbers. A subcluster detection test confirmed the presence of at least two distinct chemical compositions in samples from both lots, rejecting the null hypothesis that the groups have the same scale and location. While these spectrometric results do not conclusively prove an excess level of impurities or adulteration, they suggest that the manufacturing process may have been operating outside of a state of process control. These findings highlight the need for further investigation into potential process control issues to ensure consistent manufacturing processes and maintain drug quality and efficacy.

This study employed Fourier Transform near-infrared spectrometry to assess the quality of vecuronium bromide, a neuromuscular blocking agent. Spectral data from two lots of vecuronium were collected and analyzed using the BEST metric, principal component analysis (PCA) and other statistical techniques. The results showed that there was variability between the two lots and within each lot. Several outliers in the spectral data suggested potential differences in the chemical composition or sample condition of the vials. The outliers were identified and their spectral features were examined. A total of eight unique outliers were found in the PC space from PCs 1 to 9, so 22% of the total vials were outliers. The study findings suggest that the manufacturing process of vecuronium bromide may have been operating outside of a state of process control. Further investigation is needed to determine the source of these variations and their impact on the safety and efficacy of the drug product.

Dantrolene sodium is a direct-acting skeletal muscle relaxant. Dantrolene sodium for injection is indicated, along with suitable supportive measures, for the management of sudden, severe hypermetabolism of skeletal muscle typical of malignant hyperthermia crises in patients of any age. The formulation scanned in this work was designed to be injected intravenously. Intra-lot and inter-lot variability in the spectra of REVONTO^™ (dantrolene sodium) was measured in the Drug Quality Study (DQS) using Fourier transform near-infrared spectrometry (FTNIR). Spectra of 69 vials from lot 20REV01A contained two groups (n₁=56 vials, n₂=13 vials) when scanned with an FTNIR. The two groups of spectra in lot 20REV01A were found to be 66.7 SDs apart using a subcluster detection test, suggesting that the two groups were manufactured differently. As a result, all available samples of dantrolene were examined. A library of spectra of 141 vials of dantrolene from 4 lots were found to contain 3 separate groups, also suggesting that different vials contain different materials.