Abstract：
:The N-terminal glutamic acid (Glu) can be cyclized to form pyroglutamate (pGlu). Recent studies have suggested that N-terminal pGlu formation is an important posttranslational or co-translational event and is greatly facilitated by the enzyme glutaminyl cyclase, although the impact of the N-terminal cyclization on the potency and overall stability of mAbs is not been well known. Since most recombinant monoclonal antibodies (mAbs) contain glutamic acid and/or glutamine at their N-terminus, understanding the cyclization mechanisms may shed light on the factors that control the pGlu formation in therapeutic mAb development. Here, two mass spectrometry-based techniques were developed to investigate N-pyroglutamyl formation and the high conversion rate to pGlu at the N-terminus of the mAb was reported in the formulation development. The pGlu formation is favored at pH 4 and 8, but is less common at the neutral pH that is optimum for the enzymatic Glu conversion. These observations suggest that pGlu formation can proceed non-enzymatically at mild conditions and that this cyclization is not driven by glutaminyl cyclase in non-physiological conditions. We also calculate the half-lives of the N-terminal Glu at different pH and temperatures from the kinetics data, which would be very helpful for predicting pGlu formation and for selecting proper formulation and storage conditions.
journal_name
J Pharm Biomed Analjournal_title
Journal of pharmaceutical and biomedical analysisauthors
Yu L,Vizel A,Huff MB,Young M,Remmele RL Jr,He Bdoi
10.1016/j.jpba.2006.05.008subject
Has Abstractpub_date
2006-10-11 00:00:00pages
455-63issue
4eissn
0731-7085issn
1873-264Xpii
S0731-7085(06)00364-5journal_volume
42pub_type
杂志文章abstract：:Puerariae Radix was a widely used herbal medicine. Pueraria lobata (PL) and Pueraria thomsonii (PT) were the two authorized sources of Puerariae Radix (gegen) in China. In this study, metabolic differentiations between these two species were investigated using NMR spectroscopy followed by principal components analysis...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2013.05.017
更新日期：2014-05-01 00:00:00
abstract：:Monitoring amino acids and vitamins is important for understanding human health, food nutrition and the culture of mammalian cells used to produce therapeutic proteins in biotechnology. A method including ion pairing reversed-phase liquid chromatography with tandem mass spectrometry was developed and optimized to quan...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2015.08.036
更新日期：2016-01-05 00:00:00
abstract：:A chiral liquid chromatographic method was developed for the enantiomeric resolution of Pramipexole dihydrochloride monohydrate, (S)-2-amino-4,5,6,7-tetra-hydro-6-(propylamino) benzothiazole dihydrochloride monohydrate, a dopamine agonist in bulk drugs. The enantiomers of Pramipexole dihydrochloride monohydrate were r...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2006.02.024
更新日期：2006-06-16 00:00:00
abstract：:In the series of our previous reports, we showed that some cancer cell lines specifically express polylactosamine-type N-glycans and such glycans were often modified with fucose and sulfate residues. To confirm the proteins expressing these glycans, glycopeptide mixture obtained by digestion of whole protein fractions...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2012.06.035
更新日期：2012-11-01 00:00:00
abstract：:A new agar-free bioautographic assay for xanthine oxidase (XO) inhibitors and superoxide scavengers on TLC layers was developed and validated. Compared to the first version of TLC bioautographic agar overlay method, our bioautographic assay greatly improved the sensitivity and quantification ability. The limit of dete...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2017.11.077
更新日期：2018-02-20 00:00:00
abstract：:Species-specific acid-base and partition equilibrium constants were experimentally determined for the therapeutically important semisynthetic opioid receptor agonist hydromorphone, dihydromorphine, and mixed agonist-antagonist nalorphine and nalbuphine. The acid-base microequilibria were characterized by combining pH-...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2016.12.014
更新日期：2017-02-20 00:00:00
abstract：:Inductively coupled plasma mass spectrometry (ICP-MS) technique was used to analyze the contamination of selected 20 metals in 32 samples of honeybee venom and to demonstrate differences in the content of these elements. Among the analyzed metal microelements (Al, Co, Cu, Zn, Mn, Mo, B, V, Sr and Ni), macro-elements (...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2008.05.033
更新日期：2008-11-04 00:00:00
abstract：:Juglone (JL), as one of the major bioactive components present in the bark of Juglans mandshruica Maxim, exhibits versatile bioactivities, especially anti-cancer activity. To better understand the pharmacokinetic properties of juglone, the protein binding rate of juglone was determined by ultrafiltration method, and t...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2017.03.036
更新日期：2017-07-15 00:00:00
abstract：:DuP 747, a selective kappa agonist analgesic, was found to have at least two polymorphic forms, and this was confirmed by X-ray powder diffraction. DSC and thermomicroscopic studies indicated the polymorphic pair to be monotropic. Solubility studies suggested the relative stability of the two forms to be similar. The ...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/0731-7085(94)e0002-i
更新日期：1994-06-01 00:00:00
abstract：:An analytical methodology using square wave voltammetry (SWV) at a hanging mercury drop electrode (HMDE) was developed for the quantitative determination of dipyridamole (DIP), a drug used for the treatment of several cardiovascular diseases, in pharmaceutical tablets and injections of Persantin in phosphate buffer (p...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2004.09.011
更新日期：2005-01-04 00:00:00
abstract：:A simple, specific and sensitive high-performance liquid chromatographic (HPLC) method has been developed for the assay of fluvoxamine in human plasma and urine. The method was based on reaction of fluvoxamine with 1,2-naphthoquinone-4-sulphonic acid sodium salt (NQS) forming orange colored product. The fluvoxamine-NQ...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2006.11.005
更新日期：2007-03-12 00:00:00
abstract：:Elderly people represent about the 15% of the total world population and often include a polymedicated age group with an average consumption of 5-10 pills per day. The main pharmaceuticals consumed are antianalgesics, antidiabetics, anti-parkinson compounds, anti-convulsants, drugs to treat constipation and drugs to t...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2019.02.016
更新日期：2019-05-10 00:00:00
abstract：:Benzodiazepines (BDZ) and z-drugs belong to the most frequently prescribed medicines worldwide used for anxiety, epilepsy and sleeping disorders. Due to their pharmacology, they have a high potential for misuse. Hair analysis is being performed for the retrospective monitoring of drug exposure. However, there is a lac...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2020.113151
更新日期：2020-05-10 00:00:00
abstract：:Red yeast rice (RYR) is prepared by fermenting rice with various strains of the yeast Monascus spp of the Aspergillaceae family. Depending on the Monascus strains and the fermentation conditions, the products may contain monacolins, pigments and citrinin as secondary metabolites. Authentic and commercial RYR samples w...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2014.07.039
更新日期：2014-11-01 00:00:00
abstract：:A rapid and simple LC-MS/MS method was developed and validated for the simultaneous determination of coniferyl ferulate (CF) and its metabolite coniferyl alcohol (CA) using bavachromene as an internal standard (IS). A TSQ Quantum Access mass spectrometer was operated under selected-reaction monitoring mode using negat...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2017.08.033
更新日期：2017-11-30 00:00:00
abstract：:A high performance liquid chromatography (HPLC) method for the detection of traces of LpHse (4-tert-amylphenol and 2-phenylphenol) has been developed and validated. The method was shown to be linear in the range from 0.5 to 10.00 ppm in solution. The method was also shown to be accurate with a recovery of up to 95% by...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2005.10.049
更新日期：2006-05-03 00:00:00
abstract：:A simple, rapid, reliable and sensitive ultra-high performance liquid chromatography tandem spectrometry (UHPLC-MS/MS) method was established for determination of eight serum protein-bound uremic toxins (hippuric acid, indoxyl sulfate, indole-3-acetic acid, kynurenic acid, L-kynurenine, melatonin, 3-carboxy-4-methyl-5...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2020.113312
更新日期：2020-07-15 00:00:00
abstract：:The interaction between gabapentin (GP), a neuroleptic drug, and calf-thymus DNA was investigated. Cyclic voltammetry and different spectroscopic methods (UV/vis spectrophotometry, spectroflourimetry and circular dichroism) were used to study the process. The oxidation current of GP was considerably decreased in the p...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2012.06.005
更新日期：2012-11-01 00:00:00
abstract：:Therapeutic monitoring of the potent, highly lipophilic glucocorticoid, fluticasone propionate (FP), was initially performed by a radioimmunoassay method. However an improved method with a lower limit of quantitation (LLOQ) of at least 25 pg per ml (pg/ml(-1)) was needed to measure the low levels of FP present in huma...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/s0731-7085(99)00213-7
更新日期：1999-12-01 00:00:00
abstract：:The lignan (-)-grandisin has shown important pharmacological activities, such as citotoxicity and antiangiogenic, antibacterial and trypanocidal activities. So, it has been considered as a potential drug candidate. In the early drug development process, drug metabolism is one of the main parameters that should be eval...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2012.08.028
更新日期：2013-01-01 00:00:00
abstract：:Despite significant analytical improvements during this last decade, characterizing the whole integrity of monoclonal antibodies during their bioproduction remains a challenge. In this study, we report a new analytical approach to evaluate the overall heterogeneity/integrity of mAbs by LC-MS after combined proteolysis...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2017.11.046
更新日期：2018-02-05 00:00:00
abstract：:Bisphosphonates (BPs) have broad medical applications against osteoporosis, bone metastasis and Paget's disease. The BP-related jaw osteonecrosis limits their use extensively and has a causal relationship with the process of drug disposition, such as deposition on bone and slow elimination rate. Thus it is imperative ...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2020.113579
更新日期：2020-10-25 00:00:00
abstract：:The solution-phase hydrolysis kinetics of the Aprepitant (Emend) prodrug, Fosaprepitant Dimeglumine, were investigated using an HPLC chromatographic reactor approach. The term 'chromatographic reactor' refers to the use of an analytical-scale column as both a flow-through reactor and, simultaneously, as separation med...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2006.02.005
更新日期：2006-06-07 00:00:00
abstract：:An NMR-based metabolomics approach was conducted to holisticly explore the effect of XFZYD (a traditional Chinese medicine formula) on high-fat diet induced hyperlipidemia rats with one of the commonly used antihyperlipidemic agents, simvastatin as the positive control. NMR spectra from blood plasma combined with stat...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2013.02.014
更新日期：2013-05-05 00:00:00
abstract：:Guggulipid is known to be useful for hypercholesterolemia, arthritis, acne, and obesity. These activities are attributed to its two principal isomeric active constituents, viz., E- and Z-guggulsterones. There are several side effects reported for guggulipid, which include widespread erythematous papules in a morbillif...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2020.113275
更新日期：2020-07-15 00:00:00
abstract：:Two monoglucuronides (CA1G1 and CA1G2) of the catecholic cis-stilbene Combretastatin A1 (CA1, OXi4500), have been identified in a clinical trial of the bisphosphate prodrug of OXi4500, OXi4503. A validated assay for the two glucuronides in human plasma using HPLC with fluorescence detection after post-column photolysi...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2011.12.022
更新日期：2012-03-25 00:00:00
abstract：:In traditional Chinese medicine practice, crude herbs are often subjected to traditional processing (Paozhi in Chinese) for a special medicinal purpose. Bran-frying is one of processing methods for Paeoniae Radix Alba (PRA). Previous studies found that paeoniflorin and paeoniflorin sulfonate, a principle bioactive com...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2018.07.003
更新日期：2018-09-10 00:00:00
abstract：:In this work, an ionic liquid-based ultrasonic-assisted extraction (ILUAE) method was developed to extract caffeoylquinic acids (CQAs) from Flos Lonicerae Japonicae (FLJ). ILUAE parameters were optimized by response surface methodology, including IL concentration, ultrasonic time, and liquid-solid ratio. Optimized ILU...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/j.jpba.2015.12.019
更新日期：2016-02-20 00:00:00
abstract：:LC assays utilizing fully automated sample preparation procedures on Zymark PyTechnology Robot and BenchMate Workstation for the quantification of hydrochlorothiazide (HCTZ) in human plasma and urine have been developed. After aliquoting plasma and urine samples, and adding internal standard (IS) manually, the robot e...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/0731-7085(94)00096-4
更新日期：1994-12-01 00:00:00
abstract：:The HPLC method for simultaneous determination of cetylpyridinium chloride (CPC), tetracaine hydrochloride (TTC) in Xipiluan buccal tablets was developed and validated. The HPLC method was performed on a CN column (150 x 4.6 mm i.d., 5 microm particle size); the mobile phase was methanol-tetramethylammonium hydroxide ...
journal_title：Journal of pharmaceutical and biomedical analysis
pub_type： 杂志文章
doi：10.1016/s0731-7085(03)00108-0
更新日期：2003-06-01 00:00:00
