Robust Heartbeat Detection From Multimodal Data via CNN-Based Generalizable Information Fusion.

OBJECTIVE: Heartbeat detection remains central to cardiac disease diagnosis and management, and is traditionally performed based on electrocardiogram (ECG). To improve robustness and accuracy of detection, especially, in certain critical-care scenarios, the use of additional physiological signals such as arterial blood pressure (BP) has recently been suggested. Therefore, estimation of heartbeat location requires information fusion from multiple signals. However, reported efforts in this direction often obtain multimodal estimates somewhat indirectly, by voting among separately obtained signal-specific intermediate estimates. In contrast, we propose to directly fuse information from multiple signals without requiring intermediate estimates, and thence estimate heartbeat location in a robust manner. METHOD: We propose as a heartbeat detector, a convolutional neural network (CNN) that learns fused features from multiple physiological signals. This method eliminates the need for hand-picked signal-specific features and ad hoc fusion schemes. Furthermore, being data-driven, the same algorithm learns suitable features from arbitrary set of signals. RESULTS: Using ECG and BP signals of PhysioNet 2014 Challenge database, we obtained a score of 94%. Furthermore, using two ECG channels of MIT-BIH arrhythmia database, we scored 99.92%. Both those scores compare favorably with previously reported database-specific results. Also, our detector achieved high accuracy in a variety of clinical conditions. CONCLUSION: The proposed CNN-based information fusion (CIF) algorithm is generalizable, robust and efficient in detecting heartbeat location from multiple signals. SIGNIFICANCE: In medical signal monitoring systems, our technique would accurately estimate heartbeat locations even when only a subset of channels are reliable.

Determination of Alkyl Methanesulfonates in Doxazosin Mesylate by Gas Chromatography-mass Spectrometer.

High sensitive rapid gas chromatography-mass spectrometry method for the determination of four carcinogenic alkyl methanesulfonates viz. methyl methanesulfonate, ethyl methanesulfonate, isopropyl methanesulfonate and n-butyl methanesulfonate in doxazosin mesylate has been presented by using selective ion monitoring mode. The optimum separation was achieved between methyl methanesulfonate, ethyl methanesulfonate, isopropyl methanesulfonate and n-butyl methanesulfonate on a DB-5 (30 m×0.32 mm×1.0 µm) capillary column under programming temperature. Acetonitrile, water and ammonia (90:9:1 v/v/v) mixture was used as diluent. Various factors involved in the gas chromatography-mass spectrometry method development are also presented. This method was validated as per International Conference on Harmonization guidelines. The limit of quantitation of methyl methanesulfonate, ethyl methanesulfonate, isopropyl methanesulfonate and n-butyl methanesulfonate is 6 ppm with respect to 30 mg/ml of doxazosin mesylate.

Application of oxidative coupling reactions for the estimation of ritodrine hydrochloride in bulk sample and dosage forms.

Three simple and sensitive visible spectrophotometric methods (M(1), M(2) and M(3)) have been described for the estimation of ritodrine hydrochloride (RTH) in pure state and in unit dosage forms. These are based on the oxidative coupling reaction of RTH, with 3-methyl benzothiazolione hydrazone (MBTH) in the presence of cerium 1V (Ce IV) (Method M(1)), N,N-dimethylamino-paraphenylenediamine (DMPD) in the presence of chloramine-T (CAT) (Method M(2)) and 4-aminophenazone (4-AP) in the presence of [Fe(CN(6))](3-) (Method M(3)). The variable parameters in all these methods have been optimised and the chemical reactions involved are presented. The results obtained in the three methods are statistically validated and recoveries range from 99.7 to 101.3%.

Spectrophotometric determination of astemizole.

Four simple and sensitive spectrophotometric methods for the determination of astemizole (AZ) in pure samples and pharmaceutical formulations are described. They are based on the oxidation of astemizole with excess N-bormosuccinimide (NBS) and determination of the unconsumed NBS with, metol-sulphanilamide (method A, lambda(max): 520 nm) or celestine blue (method B, lambda(max): 540 nm); or by the reduction of Folin-ciocalteu reagent (method C, lambda(max): 720 nm); or by the formation of a chloroform-soluble, coloured ion-association complex between the drug and azocarmine G (AG) at pH 1.5 (method D, lambda(max); 540 nm). The results obtained are reproducible with a coefficient of variation of less than 1.0%.

New spectrophotometric method for the determination of some drugs with iodine and wool fast blue BL.

A simple, sensitive and selective method is proposed for the spectrophotometric determination of drugs, viz. ampicillin, penicillin V, amoxycillin, cloxacillin, cefadroxil, ceftezoxime, griseofulvin, streptomycin, nicoumalone and acebutolol HCl, based on their reactivity with iodine. The method involves the addition of excess iodine of known concentration to the drug in the presence of NaOH and the unreacted iodine is determined by the measurement of the decrease in the absorbance of the dye wool fast blue BL (lambda(max)=540 nm) which was found to be the most suitable of several dyes tested. This method was applied for the determination of drug contents in pharmaceutical formulations and enabled the determination of the drugs in microgram quantities (0.8-9.6 mug ml(-1)). No interferences were observed from excipients and the validity of the method was tested against reference methods.

Determination of pentoxifylline in pharmaceutical formulations using iodine as oxidizing agent.

Simple, selective and sensitive spectrophotometric methods are described for the determination of pentoxifylline, based on the haloform reaction with a known and excess of standard iodine solution under alkaline conditions. The excess of iodine is determined at pH 3.0 with metol-isoniazid (lambda(max)=620 nm; method A) or wool fast blue BL (lambda(max)=540 nm, method B). All the variables have been optimised and the reaction mechanisms presented. Regression analysis of Beer's law plots showed good correlation in the concentration ranges 4.0-24.0 and 0.4-2.4 mg ml(-1) for methods A and B respectively. No interferences were observed from excipients and the validity of the methods was tested by analysing pharmaceutical formulations. Recoveries were 99.0-100.0%. The concentration measurements were reproducible within a relative standard deviation of 1.0%.

Application of sodium metaperiodate for the determination of ribavirin in pharmaceutical formulations.

Three simple and sensitive visible spectrophotometric methods (A-C) have been described for the assay of ribavirin either in pure form or in pharmaceutical formulations. They are based on the oxidation of ribavirin with excess sodium metaperiodate and estimating either the products formed (dialdehyde with MBTH, method A; iodate with metol-sulphanilamide, in the presence of Mo(VI) and iodide, method B) or the amount of periodate consumed (celestine blue in the presence of telurium (IV), method C). All of the variables have been optimized and the reaction mechanisms presented. The concentration measurements are reproducible within a R.S.D. of 1.0%. Recoveries are 99.2-101.2%.

Spectrophotometric methods for the determination of omeprazole in bulk form and pharmaceutical formulations.

Four simple and sensitive methods for the assay of omeprazole (OMZ) were developed. These methods are based on the formation of colored species by treating OMZ with 3-methyl-2-benzothiazolinone hydrazone (MBTH) following oxidation with ferric chloride (method A) or m-aminophenol following oxidation with chloramine-T (CAT) (method B) or Folin-Ciocalteau reagent (FC) (method D), or by oxidizing OMZ with excess N-bromosuccinimide (NBS) and determining the consumed NBS with a decrease in color intensity of Celestine blue (CB) (method C). All variables have been optimized. Regression analysis of Beer's plots showed good correlation in the concentration range of 1.0-10, 2.0-32, 0.4-2.4 and 0.8-10 mug ml(-1) for methods A, B, C and D, respectively. No interference was observed for formulation additives and the validity of each method was tested by analysing capsules containing OMZ. Recoveries were 98.7-100.1%.

Assay of cisapride in pharmaceutical formulations by extraction spectrophotometry.

Four simple and sensitive spectrophotometric methods (A-D) for the assay of cisapride in pure and dosage forms based on the formation of chloroform soluble ion-associates under specified experimental conditions are described. Four acidic dyes, namely, Suprachen Violet 3B (SV 3B, method A), Erioglaucine A (EG-A, method B), Naphthalene Blue 12 BR (NB-12BR, method C) and Tropaeolin 000 (TP 000, method D) are utilized. The extracts of the ion-associates exhibit absorption maxima at 595, 640, 620 and 500 nm for methods A, B, C and D, respectively. Beer's law and the precision and accuracy of the methods are checked by the UV reference method. The results are reproducible with an accuracy of +/-1.0%. The methods are found to be suitable for the determination of cisapride in the presence of the other ingredients that are usually present in dosage forms.

Determination of doxorubicin hydrochloride by visible spectrophotometry.

Four simple and sensitive visible spectrophotometric methods (A-D) have been described for the assay of doxorubicin hydrochloride either in pure form or in pharmaceutical formulations. Method A was developed based on oxidation of the drug with Fe(III) to produce Fe(II), which subsequently reacts with 1.10-ortho-phenanthroline to form a red colored complex (lambda(max): 510 nm) at pH 4.6. Method B involves the reduction of Folin-Ciocalteu (F-C) reagent by the drug and the reduced species formed possesses a characteristic intense blue color (lambda(max): 770 nm). In methods C and D. oxidation of the drug with periodate at specified experimental conditions yields formaldehyde and dialdehyde, which in turn react either with 3-methyl-2-benzothiazolinone hydrazone hydrochloride to form an intensely brilliant blue cationic dye (lambda(max): 620-670 nm. method C) or by condensation with phenylhydrazine hydrochloride (PHH) to form orange-red colored product (lambda(max): 510 nm, method D) in the presence of potassium ferricyanide. All of the variables have been optimized and the reaction mechanisms presented. The concentration measurements are reproducible within a relative standard deviation of 1.0%.

Spectrophotometric methods for the determination of prazosin hydrochloride in tablets.

Four simple and sensitive methods for the assay of prazosin hydrochloride (PRH) are developed. These methods are based on the formation of coloured species by treating it either with excess N-bromosuccinimide (NBS) and determining the unconsumed NBS with p-N-methyl aminophenol sulphate (metol)-sulphanilamide (SA) reagent (method A, lambda(max) 520 nm): with 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) in the presence of eerie ammonium sulphate (CAS) (method B, lambda(max) 620 nm) or with acidic dyes such as orange-II (O-II) (method C, lambda(max) 490 nm) and alizarin violet 3B (AV-3B) (method D, lambda(max) 570 nm) under the specified experimental conditions. Regression analysis of Beer's law plot showed good correlation in the concentration range of 1.0-10.0, 2.5-25.0, 1.0-17.5 and 2.5-30.0 mug ml for methods A, B, C and D respectively.

Spectrophotometric determination of bio-active compounds with chloramine-T and gallocyanine.

A simple, sensitive and selective method for the spectrophotometric determination of drugs, viz., sulphamethoxazole, tetracycline HCl, amidopyrine, nifurtimox and isoniazid and biologically important amino acids, cysteine, aspartic acid and arginine based on their reactivity with chloramine-T (CAT) is proposed. The method involves the addition of excess CAT of a known concentration in the presence of 0.25 M HCl and the determination of the unreacted CAT by measurement of the decrease in the absorbance of the dye, gallocyanine (lambda(max): 540 nm), the most suitable of several dyes that were tested. This method was applied to the determination of drug contents in pharmaceutical formulations and to the measurement of the aspartic acid content of some protein hydrolysates. The method is useful for the determination of the target compounds in microgram quantities from 0.4-5.6 microg mL(-1) with the exceptions of arginine (1.0-8.0 microg mL(-1)) and nifurtimox (0.8-5.6 microg mL(-1)). Standard deviations were typically 0.5 mg per dose (RSD 0.5-1.2%). No interferences were observed from common excipients in formulations, and detailed interference studies of other amino acids in the determination of cysteine, aspartic acid and arginine are reported. The validity of the method was tested against spectrophotometric and titrimetric reference methods. Recoveries were 99.8-102.1%.

Spectrophotometric methods for the determination of tamoxifen citrate.

Three simple and sensitive spectrophotometric methods for the determination of tamoxifen citrate have been developed. They are based on the formation of an ion-association complex between the drug and a dye, Erioglaucine A, which is extractable into chloroform and has an absorption maximum at 625 nm (method A), oxidation with excess potassium permanganate and the determination of unconsumed permanganate using Fast Green FCF (method B), or by the formation of a coloured cobalt thiocyante coordination complex which is extracted into benzene and measured at 635 nm (method C). Beer's law limits for methods A, B, and C are 0.5-3.0 mug ml(-1), 1.0-6.0 mug ml(-1) and 100-500 mug ml(-1), respectively. No interference was observed from tableting additives and the applicability of the methods was examined by analysing tablets containing tamoxifen. The quantities determined were 99.0-100.03% of the exptected values.

Extractive spectrophotometric determination of some fluoroquinolone derivatives in pure and dosage forms.

Two simple and sensitive extractive spectrophotometric methods for the determination of some fluoroquinolone derivatives (norfloxacin, NRF; ciprofloxacin, CPF; ofloxacin, OFL; and enrofloxacin, ERF) with Supracene Violet 3B (SV 3B, method A) and tropaeolin 000 (TP 000, method B) are described. The methods are based on the formation of ion-association complexes of fluoroquinolones with these dyes, which are extracted into chloroform and have absorption maxima at 575 nm (SV 3B) and 485 nm (TP 000). The methods obey Beer's law and the precision and accuracy of the methods were checked by UV reference methods. The detection limits were 5.0 mug/ml for NRF and 2.5 mug/ml for CPF in method A and 2.5 mug/ml for OFL and ERF in methods A and B.

Spectrophotometric methods for the determination of nifurtimox in bulk form and pharmaceutical formulations.

Three simple and sensitive methods for the assay of Nifurtimox (NIF) which is an active antitrypanocide were developed. These methods are based on the formation of coloured species by treating either its reduction product with 3-methyl-2-benzothiazolinone hydrazone (MBTH) in the presence of ferric chloride (method A) or its hydrolysis product with 2-thiobarbituric acid (TBA) (method B) or by oxidizing it with excess N-bromosuccinamide (NBS) and determining the consumed NBS using p-N-methylaminophenol sulphate (metol)-isonicotinic acid hydrazide (INH) (method C). All variables have been optimized and the reaction mechanisms presented. Regression analysis of Beer's plot showed good correlation in the concentration range of 2.5-10, 2.5-30 and 1.25-7.5 microg/ml for methods A, B and C, respectively. No interference was observed from the additives and the validity of the methods was tested by analysing the tablets. Recoveries were 99.2-100.9%.

Evaluation of astemizole purity by HPLC.

A liquid chromatographic method is described for the evaluation of Astemizole purity. The method is also applicable for the analysis of pharmaceutical dosage forms of Astemizole using indole as internal standard. Separation was achieved with a micro bondapak C(18) column and phosphate buffer (pH 6.0):acetonitrile (50:50 v/v) as eluent, at a flow rate of 1.5 ml/min with UV detection at 280 nm. The method is suitable for estimating the possible impurities if any present in Astemizole up to 0.05% for 1a and 0.25% for 1b. The method is simple, rapid and accurate for the analysis of Astemizole.

Spectrophotometric methods for the determination of tolnaftate.

Two simple and sensitive visible spectrophotometric methods (methods A and B) for the determination of tolnaftate in bulk samples and formulations are described. Method A (lambda(max) 490 nm) involves the reaction of tolnaftate with 2,6-dichloroquinone-4-chlorimide (DCQC: Gibb's reagent), while method B (lambda(max) 530 nm) is based on a similar reaction of the drug with p-N,N-dimethylphenylene diamine in the presence of chloramine-T. Both these methods are applicable to pure samples as well as formulations of the drug.

Three simple spectrophotometric methods for the determination of sulphinpyrazone.

Three simple and sensitive spectrophotometric methods for the determination of sulphinpyrazone (SP) in bulk samples and pharmaceutical formulations are described. They are based on the oxidation of sulphinpyrazone with excess N-bromosuccinimide (NBS) and determination of the unconsumed NBS with metol-isonicotinic acid hydrazide (method A, lambda(max): 620 nm); by the reduction of Folin-Ciocalteu reagent (method B, lambda(max) 770 nm); or by the formation of a chloroform-soluble, coloured ion-association complex between the drug and Methylene Violet (MV) at pH 7.0 (method C, lambda(max) 545 nm).

Micro-determination of warfarin sodium, nicoumalone and acebutolol hydrochloride in pharmaceutical preparations.

A simple, selective and sensitive spectrophotometric method has been developed for the determination of microgram quantities of warfarin sodium (WS), nicoumalone (NIC) and acebutolol hydrochloride (ACBH), either in pure form or in pharmaceutical preparations. This method is based on the haloform reaction with a known and excess of standard iodine solution under alkaline conditions. The excess of iodine is determined at pH 3.0 with metol-INH. The absorbance of the resulting p-N-methyl-benzoquinonemonoimine-INH charge-transfer complex is measured at 620 nm.

Spectrophotometric determination of nicoumalone, acebutolol hydrochloride and procainamide hydrochloride.

A sensitive spectrophotometric method is described for the determination of nicoumalone (NIC), acebutolol hydrochloride (ACBH) or procainamide hydrochloride (PAH) either in pure form or in pharmaceutical formulations. The method is based on the oxidative coupling reaction through the involvement of an aromatic primary amino group (released through reduction in NIC or hydrolysis in ACBH or existing free in PAH) in the drug with 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) in the presence of ferric chloride [Fe(III)]. The resulting chromophores are measured at 620 nm for NIC and ACBH and 580 nm for PAH. The concentration measurements are reproducible within a relative standard deviation of 1%.