Plasma monkey

High performance liquid chromatography-mass spectrometric methods Nitin et al. [75] developed and validated a sensitive and selective liquid chromatography-tandem mass spectrometric method (LC MS MS) for the simultaneous estimation of bulaquine and its metabolites primaquine in monkey plasma. The mobile phase consisted of acetonitrile ammonium acetate buffer (20 mM, pH 6) (50 50, v/v) at a flow rate of 1 mL/min. The chromatographic separations were achieved on two Spheri cyano columns (5 pm, 30 cm x 4.6 mm), connected in... 

Dai S. et al., 2005. Quantitation of sifuvirtide in monkey plasma by an online solid-phase extraction procedure combined with liquid chromatography/electrospray ionization tandem mass spectrometry. Rapid Commun Mass Spectrom 19 1273. 

Hsieh Y. et al., 2001. Quantitative screening and matrix effect studies of drug discovery compounds in monkey plasma using fast-gradient liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 15 2481. 

These three analogues are more metabolically stable than LHRH. Thus, the half-life of nafarelin in monkeys and rats after i.v. administration was four to five times longer than that of LHRH [214], When incubated in monkey plasma, LHRH was readily degraded (f1/2 ca. 2 h), whereas nafarelin was more resistant (tm> 160 h). The metabolism of [14C]nafarelin was also investigated in humans following subcutaneous administration [215]. As shown in Fig. 6.39, the first metabolic steps were cleavage in the 4-5, 5-6, and 7-8 positions. Because of the presence of the 14C-label, the fate of D-2-Nal could be carefully monitored. The same metabolic pattern was observed in the rhesus monkey [216]. 

Vinyl bromide is readily absorbed upon inhalation by rats and showed an 11-fold accumulation within the rats compared with the concentration in gaseous phase. Metabolism is saturable at exposure concentrations greater than 250 mg/mT Following inhalation of vinyl bromide by rats, rabbits and monkeys, plasma levels of nonvolatile bromide increased with exposure duration, and more rapidly in phenobarbital-pretreated rats. 

Hsieh, Y., Chintala, M., Mei, H., Agans, J., Brisson, J. M., Ng, K., and Korfmacher, W. A. (2001). Quantitative screening and matrix effect studies of drug discovery compounds in monkey plasma [by] using fast-gradient liquid chromatography/tandem mass spectrometry. Rapid Commun. Mass Spectrom. 15 2481-2487. 

Clarke, N., Rindgen, D., Grotz, D., and Cox, K. (2002). Detection and identification of atoxic metabolite from monkey plasma. In Proceeding of the 50th ASMS Conference on Mass Spectrometry and Allied Topics, Orlando, EL. 

Drug X is an Ab against a target macromolecule Y . An ELISA method was developed and validated for the determination of X in human and monkey plasma. Since the purposes of these methods were to support preclinical and clinical PK studies, the method validation and sample assays were conducted under an in-house SOP, which is GLP-compliant with IA considerations according to De-Silva et al. [10]. 

In order to assess matrix effects, spike-recovery experiments were performed on samples from 10 individual human and six monkey matrix lots. Human samples were spiked with concentrations at the LLOQ and 10-fold the LLOQ. Monkey samples were spiked with concentrations at the LLOQ, two- and 400-fold the LLOQ. The results of the spike-recovery experiments are shown in Table 6.2. Some unspiked human samples showed a substantial amount of X, and their values were subtracted from the spiked sample results before calculating the spike recovery. For samples from monkey plasma samples, all samples were blank and no correc-... 

Previous applications of ESI-MS could quantify intact proteins at relatively high concentrations, such as that of human transferrin in plasma samples [79] and o ,-globulin in urine and kidney samples [80]. With the use of solid-phase extraction combined with a high-sensitivity MS, improvements on sensitivity were achieved, for example for the quantification of rk5 in monkey plasma reaching a LLOQ of 10.29 ng/mL [81]. 

Fig. 10.4 Monkey plasma and tissue bioavailabilities (BAV) determined by either an intravenous (IV) or subcutaneous (SC) AUC baseline after seven daily intrajejunal administrations of ISIS 104838. Note that the plasma BAV was more in line with tissue(s) for the SC-based data.

Qian and Gallo used HPLC to determine nimodipine in monkey plasma [31]. After extraction with ethyl acetate and evaporating the organic phase to dryness, the residue was dissolved in the mobile phase (aqueous 65% methanol). A Hypersil ODS column (15 cm x 4.6 mm i.d.) was used. The mobile phase flow rate was 1 mL/min, and detection was effected at 238 nm. The calibration graph was linear over the range of 0.01-2 pg/mL, and the recovery was 95-106%. 

A precise, accurate, selective, and sensitive HPLC method for the detection of 2-ethyl-4,6,8-trimethylimidazo[l,2]pyrazolo[3,4-J]pyrimidine in monkey plasma is based on the use of two reversed-phase Cl8 Hypersil columns placed in series and UV detection at 315 nm. The method is linear over a concentration change of 0.05-3.0 fig ml 1 and the detection limit is 0.05 ng ml 1 (89JC493). 

Bakhtiar R, Khemani L, Hayes M et al. (2002) Quantification of the anti-leukemia drug ST1571 (Gleevec) and ist metabolite (CGP 74588) in monkey plasma using a semi-automated solid phase extraction procedure and liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal 28(6) 1183-1194... 

Wang, G. et al. Ultra-performanee liquid chromatography/tandem mass speetrometrie determination of diastereomers of SCH 503034 in monkey plasma. J. Chromatog. B. 2007, 852, 92-100. 

High Pressure Liquid Chromatography. In monkey plasma metabolites of thymoxamine, detection limits 2 ng for desacetylthymoxamine and 4 ng for desmethyldesacetylthymoxamine, fluorescence detection—A. E. Geahchan and P. L. Chambon, Analyt. Chem., 1980, 52, 999-1001. 

Roth JS, McCully CM, Balis EM, Poplack DG, Kelley JA. 2 -Beta-fluoro-2, 3 -dideoxyadenosine, lodenosine, in rhesus monkeys Plasma and cerebrospinal fluid pharmacokinetics and urinary disposition. Drug Me tab Dispos 1999 27 1128-32. 

In order to study the effects of chronic administration on the cognitive function of children by means of nonhuman primates, a method was developed for the determination of MPH plasma levels under chronic and acute dosing conditions [60]. MPH and ritalinic acid were isolated from plasma in SPE on Oasis HLB. LC was performed using a 15Qx2-mm-lD Cig column (3 pm) and 20% acetonitrile in 0.1% aqueous formic acid at a flow-rate of 0.2 ml/min. Positive-ion ESI-MS was performed in SIM mode on a single-quadrapole system. [Z)3]-MPH was used as ILIS. The LOQ was 0.25 ng/ml in monkey plasma. 

D.R. Doerge, C.M. Fogle, M.G. Paule, M. McCuUagh, S. Bajic, Analysis of methylphenidate and its metabolite ritalinic acid in monkey plasma by LC-ESI-ALS,... 

M.R. Anari, R. Bakhtiar, B. Zhu, S. Huskey, R.B. Franklin, D.C. Evans, Derivatization of ethinylestradiol with dansyl chloride to enhance ESI Application in its trace analysis in rhesus monkey plasma. Anal. Chem., 74 (2002) 4136. 

Doerge, D.R. Fogle, C.M. Paule, M.G. McCullagh, M. Bajic, S. Analysis of Methylphenidate and its Metabolite Ritalinic Acid in Monkey Plasma by Liquid Chromatography/Electrospray Ionization Mass Spectrometry, Rapid Commun. Mass Spectrom. 14, 610-623 (2000). 

Hsieh, Y. Brisson, J.M. Ng, K. Korfmacher, W.A. Direct Simultaneous Determination of Drug Discovery Compounds in Monkey Plasma Using Mixed-Function Column Liquid Chromatography/Tandem Mass Spectrometry, ... 

Bakhtiar, R. Khemani, L. Hayes, M. Bedman, T Tse, F. "Quantification of the Anti-Leukemia Drug ST1571 (Gleevec) and its Metabolite (CGP 74588) in Monkey Plasma Using a Semi-Automated Solid Phase Extraction Procedure and Liquid Chromatography-Tandem Mass Spectrometry, J. Pharm. Biomed. Anal. 28, 1183-1194 (2002). 

Effect of anticoagulants on curve in cynomolgus monkey plasma... 

FIGURE 9.2 A comparison of two calibration curves in cynomolgus monkey plasma. One curve was prepared in K3 EDTA plasma and the other in lithium heparin plasma. Each calibrator contained 2% of the corresponding matrix prepared from the same stock solution of drug, spiked directly into 100% plasma and then diluted 50 fold in assay buffer. The pH of the diluted calibrators was 7.4 for each matrix. 

The major metabolite and several other oxidative metabolites of C-ABT-VTS were isolated and purified from rat and monkey bile. As noted in the in vitro studies, the metabolic pathway was primarily oxidation, giving A-desmethyl-ABT-773 as the major metabolite and several other oxidative products as minor metabolites. In rat, dog, or monkey plasma, parent compound was the only or major component in circulating radioactivity, with M-1 as the major metabolite. The metabolic profile was similar in bile and feces with M-1, M-4 (10-hydroxy-A-desmethyl ABT-773), or M-6 (oxidation of ABT-773) as major metabolites in all species. In urine, the parent compound was the major component with M-1 as the primary metabolite [108]. 

Sample preparation Add 0.1 (rabbit) or 1 (rat, monkey) plasma to 1 mL 100 mM pH 5.0 acetate buffer and 50 jlL Glusulase (from Helix Pomatia, contains 10000 U/mL sulfatase and 90000 U/mL p-glucuronidase, DuPont), heat at 37° for 1 h, cool to room temperature, add 15 mL diethyl ether, shake mechanically at high speed for 10 min, centrifuge at 3033 g for 10 min, freeze in dry ice/acetone. Remove the organic layer and evaporate it to dryness under a stream of nitrogen, reconstitute the residue in 500 j.L mobile phase, filter (0.45 p.m), inject a 150 xL aliquot of the filtrate. 

Chandrasekaran, A. Osman, M. Adelmeui, S.J. Warsheski, J. Scatina, J. Sisenwine, S.F. Determination of 17a-dihydroequilenin in rat, rabbit and monkey plasma by high-performance liquid chromatography with fluorimetric detection. J.Chromatogr.B, 1996, 676, 69—75... 

Walmsley, L.M. Chasseaud, L.F. High-performance liquid chromatographic determination of lorazepam in monkey plasma. J.Chromatogr, 1981, 226, 155-163... 

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